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1.
Immun Inflamm Dis ; 12(6): e1317, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38869352

ABSTRACT

BACKGROUND: Numerous studies have demonstrated that Absent in Melanoma 2 (AIM2) is upregulated in aortic plaques, especially in Vascular Smooth Muscle Cells in Coronary Artery Disease (CAD), and is related to inflammasome-induced inflammation. However, the underlying mechanism of this phenomenon and the role of AIM2 in atherosclerosis remained unclear. METHODS: This study enrolled 133 CAD patients and 123 controls. We isolated Peripheral Blood Leukocytes (PBLs) and the mRNA expression of AIM2 inflammasome and its downstream genes (ASC, Caspase-1, IL-1ß, and IL-18) were detected by real-time quantitative PCR (qPCR). We assessed correlations between AIM2 expressions and clinical characteristics by multiple linear regression and spearman's correlation. The THP-1 cells cultured in poly(dA:dT), A151, interferon-gamma (IFN-γ), AG490, or JC2-11. And then the mRNA and protein levels of AIM2, ASC, Caspase-1, IL-1ß, IL-18, GSDMD, and STAT1 were analyzed by qPCR and Western blot analysis, respectively. The migration and adhesive capacity of THP-1 cells was assessed using an inverted microscope and an inverted fluorescence microscope, respectively. RESULTS: In this study, we found that expressions of components of AIM2 inflammasome and its downstream genes (ASC, Caspase-1, IL-1ß, and IL-18), were all increased in PBLs of CAD patients, which indicated the inflammasome activation. AIM2 inflammasome activation further induced pyroptosis, and stimulated migration and adhesion in monocyte cell lines, which was regulated by IFN-γ probably through JAK2/STAT1 pathway. In addition, AIM2 expressions were positively correlated with systemic inflammatory indicators as an independent risk factor for CAD. CONCLUSIONS: In conclusion, increased AIM2 expression, induced by the IFN-γ/JAK2/STAT1 signal, orientates monocytes to inflammatory status or even pyroptosis through AIM2 inflammasome activation, which is involved in the development of CAD.


Subject(s)
Coronary Artery Disease , DNA-Binding Proteins , Inflammasomes , Interferon-gamma , Janus Kinase 2 , Monocytes , Pyroptosis , STAT1 Transcription Factor , Signal Transduction , Humans , STAT1 Transcription Factor/metabolism , Coronary Artery Disease/immunology , Coronary Artery Disease/metabolism , Coronary Artery Disease/pathology , Monocytes/metabolism , Monocytes/immunology , Interferon-gamma/metabolism , Male , Inflammasomes/metabolism , Janus Kinase 2/metabolism , Janus Kinase 2/genetics , Female , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Middle Aged , THP-1 Cells , Aged
2.
J Korean Acad Nurs ; 54(2): 162-177, 2024 May.
Article in English | MEDLINE | ID: mdl-38863186

ABSTRACT

PURPOSE: This study aimed to investigate the influence of uncertainty-related factors on the health behavior of individuals with coronary artery disease (CAD) based on Mishel's uncertainty in illness theory (UIT). METHODS: We conducted a cross-sectional study and path analysis to investigate uncertainty and factors related to health behavior. The study participants were 228 CAD patients who visited the outpatient cardiology department between September 2020 and June 2021. We used SPSS 25.0 and AMOS 25.0 software to analyze the data. RESULTS: The final model demonstrated a good fit with the data. Eleven of the twelve paths were significant. Uncertainty positively affected danger and negatively affected self-efficacy and opportunity. Danger had a positive effect on perceived risk. Opportunity positively affected social support, self-efficacy, perceived benefit and intention, whereas it negatively affected perceived risk. Social support, self-efficacy, perceived benefit and intention had a positive effect on health behavior. We found that perceived benefit and intention had the most significant direct effects, whereas self-efficacy indirectly affected the relationship between uncertainty and health behavior. CONCLUSION: The path model is suitable for predicting the health behavior of CAD patients who experience uncertainty. When patients experience uncertainty, interventions to increase their self-efficacy are required first. Additionally, we need to develop programs that quickly shift to appraisal uncertainty as an opportunity, increase perceived benefits of health behavior, and improve intentions.


Subject(s)
Coronary Artery Disease , Health Behavior , Self Efficacy , Social Support , Humans , Uncertainty , Male , Female , Coronary Artery Disease/psychology , Coronary Artery Disease/pathology , Middle Aged , Cross-Sectional Studies , Aged , Surveys and Questionnaires , Intention , Adult
3.
Biomed Phys Eng Express ; 10(4)2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38806008

ABSTRACT

Atherosclerosis is a cardiovascular disease mainly caused by plaque deposition in blood vessels. Plaque comprises components such as thrombosis, fibrin, collagen, and lipid core. It plays an essential role in inducing rupture in a blood vessel. Generally, Plaque could be described as three kinds of elastic models: cellular Plaque, hypocellular Plaque, and calcified Plaque. The present study aimed to investigate the behavior of atherosclerotic plaque rupture according to different lipid cores using Fluid-Structure Interaction (FSI). The blood vessel was also varied with different thicknesses (0.05, 0.25, and 0.5 mm). In this study, FSI simulation with a cellular plaque model with various thicknesses was investigated to obtain information on plaque rupture. Results revealed that the blood vessel with Plaque having a lipid core represents higher stresses than those without a lipid core. Blood vessels' thin thickness, like a thin cap, results in more considerable than Von Mises stress. The result also suggests that even at low fracture stress, the risk of rupture due to platelet decomposition at the gap was more significant for cellular plaques.


Subject(s)
Computer Simulation , Coronary Artery Disease , Models, Cardiovascular , Plaque, Atherosclerotic , Stress, Mechanical , Humans , Plaque, Atherosclerotic/pathology , Coronary Artery Disease/pathology , Blood Vessels/pathology , Lipids/chemistry , Coronary Vessels/pathology , Elasticity
4.
PLoS One ; 19(5): e0302547, 2024.
Article in English | MEDLINE | ID: mdl-38820294

ABSTRACT

INTRODUCTION: The natural outcome of coronary plaque in acute coronary syndrome (ACS) patients with chronic kidney disease (CKD) is unique, which can be analyzed quantitatively by optical flow ratio (OFR) software. METHODS: A total of 184 ACS patients with at least one nonculprit subclinical atherosclerosis (NSA) detected by optical coherence tomography (OCT) at baseline and 1-year follow-up were divided into non-CKD group (n = 106, estimated glomerular filtration rate (eGFR)> 90 mL/(min×1.73 m2)) and mild CKD group (n = 78, 60≤eGFR<90 mL/(min×1.73 m2)). Changes of normalized total atheroma volume (TAVn) of NSA was the primary endpoint at the 1-year follow-up. RESULTS: Patients with mild CKD showed more TAVn progression of NSA than non-CKD (p = 0.019) from baseline to the 1-year follow-up, which was mainly due to an increase in calcium TAVn (p<0.001). The morphological change in the maximal calcification thickness (p = 0.026) was higher and the change in the distance from the calcified surface to the contralateral coronary media membrane (ΔC-to-M) at the maximal cross-sectional calcium area was lower (p<0.001) in mild CKD group than in non-CKD group. Mild CKD had more NSA related MACEs at the 5-year follow-up than non-CKD (30.8% vs. 5.8%, p = 0.045). CONCLUSIONS: Mild CKD patients had more plaque progression of NSA which showed the increase of calcium component with more protrusion into the lumen morphologically at the 1-year follow-up and a higher corresponding incidence of NSA-related MACEs at the 5-year follow-up. TRIAL REGISTRATION: Clinical Trial registration ClinicalTrials.gov. NCT02140801. https://classic.clinicaltrials.gov/ct2/show/NCT02140801.


Subject(s)
Acute Coronary Syndrome , Glomerular Filtration Rate , Renal Insufficiency, Chronic , Tomography, Optical Coherence , Humans , Male , Female , Acute Coronary Syndrome/pathology , Acute Coronary Syndrome/diagnostic imaging , Renal Insufficiency, Chronic/pathology , Renal Insufficiency, Chronic/complications , Middle Aged , Follow-Up Studies , Aged , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/pathology , Disease Progression , Atherosclerosis/pathology , Atherosclerosis/diagnostic imaging , Atherosclerosis/complications , Coronary Artery Disease/pathology , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/complications , Clinical Relevance
5.
Int J Mol Sci ; 25(10)2024 May 11.
Article in English | MEDLINE | ID: mdl-38791267

ABSTRACT

Cardiovascular diseases, among which includes coronary artery disease, represent one of the most important causes of mortality and morbidity worldwide. Research aimed at determining the risk factors involved recognizes a group of "traditional" risk factors, but also more recent studies identified over 100 "novel" ones which may have a role in the disease. Among the latter is the thrombophilia profile of a patient, a pathology well-established for its involvement in venous thromboembolism, but with less studied implications in arterial thrombosis. This paper reviews the literature, explaining the pathophysiology of the thrombophilia causes associated most with coronary thrombosis events. Results of several studies on the subject, including a meta-analysis with over 60,000 subjects, determined the significant involvement of factor V Leiden, prothrombin G20210A mutation, plasminogen activator inhibitor-1 and antiphospholipid syndrome in the development of coronary artery disease. The mechanisms involved are currently at different stages of research, with some already established and used as therapeutic targets.


Subject(s)
Coronary Artery Disease , Factor V , Thrombophilia , Thrombosis , Humans , Coronary Artery Disease/genetics , Coronary Artery Disease/etiology , Coronary Artery Disease/pathology , Thrombophilia/genetics , Thrombophilia/etiology , Thrombosis/genetics , Thrombosis/etiology , Thrombosis/pathology , Factor V/genetics , Prothrombin/genetics , Prothrombin/metabolism , Plasminogen Activator Inhibitor 1/genetics , Plasminogen Activator Inhibitor 1/metabolism , Risk Factors , Genetic Predisposition to Disease , Mutation
6.
Arterioscler Thromb Vasc Biol ; 44(5): 1135-1143, 2024 May.
Article in English | MEDLINE | ID: mdl-38572648

ABSTRACT

BACKGROUND: Acute coronary syndrome (ACS) involves plaque-related thrombosis, causing primary ischemic cardiomyopathy or lethal arrhythmia. We previously demonstrated a unique immune landscape of myeloid cells in the culprit plaques causing ACS by using single-cell RNA sequencing. Here, we aimed to characterize T cells in a single-cell level, assess clonal expansion of T cells, and find a therapeutic target to prevent ACS. METHODS: We obtained the culprit lesion plaques from 4 patients with chronic coronary syndrome (chronic coronary syndrome plaques) and the culprit lesion plaques from 3 patients with ACS (ACS plaques) who were candidates for percutaneous coronary intervention with directional coronary atherectomy. Live CD45+ immune cells were sorted from each pooled plaque samples and applied to the 10× platform for single-cell RNA sequencing analysis. We also extracted RNA from other 3 ACS plaque samples and conducted unbiased TCR (T-cell receptor) repertoire analysis. RESULTS: CD4+ T cells were divided into 5 distinct clusters: effector, naive, cytotoxic, CCR7+ (C-C chemokine receptor type 7) central memory, and FOXP3 (forkhead box P3)+ regulatory CD4+ T cells. The proportion of central memory CD4+ T cells was higher in the ACS plaques. Correspondingly, dendritic cells also tended to express more HLAs (human leukocyte antigens) and costimulatory molecules in the ACS plaques. The velocity analysis suggested the differentiation flow from central memory CD4+ T cells into effector CD4+ T cells and that from naive CD4+ T cells into central memory CD4+ T cells in the ACS plaques, which were not observed in the chronic coronary syndrome plaques. The bulk repertoire analysis revealed clonal expansion of TCRs in each patient with ACS and suggested that several peptides in the ACS plaques work as antigens and induced clonal expansion of CD4+ T cells. CONCLUSIONS: For the first time, we revealed single cell-level characteristics of CD4+ T cells in patients with ACS. CD4+ T cells could be therapeutic targets of ACS. REGISTRATION: URL: https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000046521; Unique identifier: UMIN000040747.


Subject(s)
Acute Coronary Syndrome , CD4-Positive T-Lymphocytes , Plaque, Atherosclerotic , Single-Cell Analysis , Humans , Acute Coronary Syndrome/immunology , Acute Coronary Syndrome/genetics , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Male , Middle Aged , Female , Aged , RNA-Seq , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/metabolism , Receptors, Antigen, T-Cell/immunology , Coronary Vessels/immunology , Coronary Vessels/pathology , Sequence Analysis, RNA , Coronary Artery Disease/immunology , Coronary Artery Disease/genetics , Coronary Artery Disease/pathology , Phenotype
7.
Methods Mol Biol ; 2803: 219-226, 2024.
Article in English | MEDLINE | ID: mdl-38676896

ABSTRACT

Coronary artery dissection (CAD) is the intimal tearing of the coronary arterial wall and can be iatrogenic, spontaneous, or traumatic in origin. CAD is a rare but challenging condition that can cause significant hemodynamic compromise. Management strategies for CAD, such as the use of mechanical circulatory support devices, are available in the clinical setting. However, the incidence, etiology, and optimal management of CAD are not well-defined, emphasizing the need for adequate animal models in preclinical studies. Large animal models provide the human-like conditions necessary for testing and development of potential treatment strategies. In this chapter, we describe a method for the creation of a CAD swine model.


Subject(s)
Aortic Dissection , Coronary Vessels , Disease Models, Animal , Vascular Diseases/congenital , Animals , Swine , Coronary Vessels/pathology , Humans , Coronary Vessel Anomalies , Vascular Diseases/etiology , Vascular Diseases/pathology , Vascular Diseases/therapy , Coronary Artery Disease/pathology
8.
Sci Rep ; 14(1): 9477, 2024 04 25.
Article in English | MEDLINE | ID: mdl-38658599

ABSTRACT

To determine the association between complement C1q and vulnerable plaque morphology among coronary artery disease (CAD) patients. We conducted a retrospective observational study of 221 CAD patients admitted to The Second Affiliated Hospital of Xi'an Jiaotong University. Intravascular optical coherence tomography was utilized to describe the culprit plaques' morphology. Using logistic regression analysis to explore the correlation between C1q and vulnerable plaques, and receiver operator characteristic (ROC) analysis assess the predictive accuracy. As reported, the complement C1q level was lower in ACS patients than CCS patients (18.25 ± 3.88 vs. 19.18 ± 4.25, P = 0.045). The low complement-C1q-level group was more prone to develop vulnerable plaques. In lipid-rich plaques, the complement C1q level was positively correlated with the thickness of fibrous cap (r = 0.480, P = 0.041). Univariate and multivariate logistic regression analyses suggested that complement C1q could be an independent contributor to plaques' vulnerability. For plaque rupture, erosion, thrombus, and cholesterol crystals, the areas under the ROC curve of complement C1q level were 0.873, 0.816, 0.785, and 0.837, respectively (P < 0.05 for all). In CAD patients, the complement C1q could be a valuable indicator of plaque vulnerability.


Subject(s)
Complement C1q , Coronary Artery Disease , Plaque, Atherosclerotic , Tomography, Optical Coherence , Humans , Tomography, Optical Coherence/methods , Male , Female , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/pathology , Middle Aged , Complement C1q/metabolism , Complement C1q/analysis , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/pathology , Aged , Retrospective Studies , ROC Curve
9.
Arterioscler Thromb Vasc Biol ; 44(6): 1330-1345, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38602103

ABSTRACT

BACKGROUND: CALCRL (calcitonin receptor-like) protein is an important mediator of the endothelial fluid shear stress response, which is associated with the genetic risk of coronary artery disease. In this study, we functionally characterized the noncoding regulatory elements carrying coronary artery disease that risks single-nucleotide polymorphisms and studied their role in the regulation of CALCRL expression in endothelial cells. METHODS: To functionally characterize the coronary artery disease single-nucleotide polymorphisms harbored around the gene CALCRL, we applied an integrative approach encompassing statistical, transcriptional (RNA-seq), and epigenetic (ATAC-seq [transposase-accessible chromatin with sequencing], chromatin immunoprecipitation assay-quantitative polymerase chain reaction, and electromobility shift assay) analyses, alongside luciferase reporter assays, and targeted gene and enhancer perturbations (siRNA and clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) in human aortic endothelial cells. RESULTS: We demonstrate that the regulatory element harboring rs880890 exhibits high enhancer activity and shows significant allelic bias. The A allele was favored over the G allele, particularly under shear stress conditions, mediated through alterations in the HSF1 (heat shock factor 1) motif and binding. CRISPR deletion of rs880890 enhancer resulted in downregulation of CALCRL expression, whereas HSF1 knockdown resulted in a significant decrease in rs880890-enhancer activity and CALCRL expression. A significant decrease in HSF1 binding to the enhancer region in endothelial cells was observed under disturbed flow compared with unidirectional flow. CALCRL knockdown and variant perturbation experiments indicated the role of CALCRL in mediating eNOS (endothelial nitric oxide synthase), APLN (apelin), angiopoietin, prostaglandins, and EDN1 (endothelin-1) signaling pathways leading to a decrease in cell proliferation, tube formation, and NO production. CONCLUSIONS: Overall, our results demonstrate the existence of an endothelial-specific HSF (heat shock factor)-regulated transcriptional enhancer that mediates CALCRL expression. A better understanding of CALCRL gene regulation and the role of single-nucleotide polymorphisms in the modulation of CALCRL expression could provide important steps toward understanding the genetic regulation of shear stress signaling responses.


Subject(s)
Calcitonin Receptor-Like Protein , Coronary Artery Disease , Endothelial Cells , Enhancer Elements, Genetic , Polymorphism, Single Nucleotide , Stress, Mechanical , Humans , Endothelial Cells/metabolism , Coronary Artery Disease/genetics , Coronary Artery Disease/metabolism , Coronary Artery Disease/pathology , Calcitonin Receptor-Like Protein/genetics , Calcitonin Receptor-Like Protein/metabolism , Heat Shock Transcription Factors/genetics , Heat Shock Transcription Factors/metabolism , Mechanotransduction, Cellular , Cells, Cultured , Gene Expression Regulation , Protein Binding , Genetic Predisposition to Disease , Binding Sites
10.
Clin Radiol ; 79(5): 386-392, 2024 May.
Article in English | MEDLINE | ID: mdl-38433042

ABSTRACT

AIM: To evaluate the prevalence, aetiology, and corresponding morbidity of coronary microvascular dysfunction (CMD) in patients with suspected myocardial ischaemia. MATERIALS AND METHODS: The present study included 115 patients with suspected myocardial ischaemia who underwent stress perfusion cardiac magnetic resonance imaging. CMD was assessed visually based on the myocardial perfusion results. The CMR-derived myocardial perfusion reserve index (MPRI) and left ventricular (LV) strain parameters obtained using the post-processing software CVI42 were employed to evaluate LV myocardial perfusion and deformation. LV strain parameters included global longitudinal, circumferential, and radial strain (GLS, GCS, and GRS), global systolic/diastolic longitudinal, circumferential, and radial strain rates (SLSR, SCSR, SRSR, DLSR, DCSR, and DRSR). RESULTS: Of the 115 patients, 12 patients were excluded and 103 patients were finally included in the study. CMD was observed in 79 % (81 patients, aged 53 ± 12 years) of patients. Regarding aetiology, 91 (88 %) patients had non-obstructive coronary artery disease (CAD), eight (8 %) had obstructive CAD, and four (4 %) had hypertrophic cardiomyopathy (HCM). The incidence of CMD was highest (100 %) in patients with HCM, followed by those with non-obstructive CAD (up to 79 %). There were no statistical differences between CMD and non-CMD groups in GCS, GRS, GLS, SRSR, SCSR, SLSR, DCSR, DRSR and DLSR. CONCLUSION: The incidence of CMD was higher in patients with signs and symptoms of ischaemia. CMD occurred with non-obstructive CAD, obstructive CAD, and HCM, with the highest prevalence of CMD in HCM.


Subject(s)
Cardiomyopathy, Hypertrophic , Coronary Artery Disease , Myocardial Ischemia , Humans , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/epidemiology , Coronary Artery Disease/pathology , Prevalence , Myocardial Ischemia/diagnostic imaging , Myocardial Ischemia/epidemiology , Myocardium/pathology , Cardiomyopathy, Hypertrophic/pathology
11.
J Cardiovasc Pharmacol ; 83(6): 547-556, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38421206

ABSTRACT

ABSTRACT: Atherosclerosis is an insidious and progressive inflammatory disease characterized by the formation of lipid-laden plaques within the intima of arterial walls with potentially devastating consequences. While rupture of vulnerable plaques has been extensively studied, a distinct mechanism known as plaque erosion (PE) has gained recognition and attention in recent years. PE, characterized by the loss of endothelial cell lining in the presence of intact fibrous cap, contributes to a significant and growing proportion of acute coronary events. However, despite a heterogeneous substrate underlying coronary thrombosis, treatment remains identical. This article provides an overview of atherosclerotic PE characteristics and its underlying mechanisms, highlights its clinical implications, and discusses potential therapeutic strategies.


Subject(s)
Plaque, Atherosclerotic , Humans , Animals , Rupture, Spontaneous , Coronary Artery Disease/therapy , Coronary Artery Disease/pathology , Atherosclerosis/pathology , Atherosclerosis/metabolism , Endothelial Cells/pathology , Endothelial Cells/metabolism
12.
Adv Med Sci ; 69(1): 56-60, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38368744

ABSTRACT

PURPOSE: Growth differentiation factor 15 (GDF-15) is a member of the transforming growth factor beta superfamily and is faintly expressed under healthy conditions. GDF-15 is markedly elevated in a variety of diseases, including coronary artery disease (CAD), atrial fibrillation and heart failure. Here, we aimed to investigate the association of GDF-15 with the extent and severity of CAD in patients with stable CAD. METHODS: We enrolled 129 patients undergoing coronary angiography for the evaluation of stable CAD in the study. SYNTAX and SYNTAX II PCI/CABG scores were calculated. The CAD (+) study group was also stratified into two groups (high and low GDF-15) with respect to the mean GDF-15 value. Correlation and regression analyses were performed for further evaluation. RESULTS: Of the 129 patients, 75 had CAD. GDF-15 values were higher in the CAD (+) group (p â€‹< â€‹0.001). The two groups were compared according to a cut-off value of 2451.77. SYNTAX and SYNTAX II PCI/CABG scores were significantly associated with the high GDF-15 group (p â€‹< â€‹0.001). Additionally, correlation analysis showed a strong positive correlation between GDF-15 and SYNTAX (r: 0.859, p â€‹< â€‹0.001), SYNTAX II PCI (r: 0.921, p â€‹< â€‹0.001) and SYNTAX II CABG (r: 0.874, p â€‹< â€‹0.001) scores. Multivariate analysis identified GDF-15 as an independent predictor of CAD. CONCLUSION: GDF-15 is an independent predictor of CAD and is associated with CAD severity in terms of SYNTAX, SYNTAX II PCI and SYNTAX II CABG scores.


Subject(s)
Coronary Angiography , Coronary Artery Disease , Growth Differentiation Factor 15 , Severity of Illness Index , Humans , Growth Differentiation Factor 15/blood , Coronary Artery Disease/pathology , Coronary Artery Disease/blood , Female , Male , Middle Aged , Aged , Biomarkers/blood , Prognosis
13.
Zhonghua Xin Xue Guan Bing Za Zhi ; 52(2): 144-149, 2024 Feb 24.
Article in Chinese | MEDLINE | ID: mdl-38326065

ABSTRACT

Objective: To explore the effects and safety of saline mixed 1∶1 with contrast medium (mixed medium) and pure heparinized saline as alternative media for optimal Optical Coherence Tomography (OCT) guided percutaneous coronary intervention (PCI). Methods: This single-center, prospective cohort study enrolled patients who underwent PCI with OCT guidance for chronic stable angina or acute coronary syndrome at the Department of Cardiology, the Second Hospital of Jilin University from October 2021 to August 2022. The target vessels were examined using OCT with three different flushing media at the same anatomical positions: contrast agent, mixed medium, and pure heparinized saline. An independent observer analyzed all imaging results and evaluated the lumen imaging quality, using the proportion of the clear imaging field (CIF%) as a quantitative measure for analysis. The average luminal diameter was compared among different flushing media. The study also assessed the image quality of the luminal anatomical structures, lesion pathologies, and stents. Results: A total of 105 patients were enrolled in the study, including 110 target vessels. The age of the enrolled patients was (60.5±8.4) years, with 60 male patients (57.1%). OCT examinations were successfully completed using all three media, and no related complications were observed in any groups. The three flushing media presented with the same image quality in terms of depicting the lumen anatomical structures, lesion characteristics, and stent-related features. The mixed medium group achieved a comparable CIF% to the contrast group with both right and left coronary arteries (right coronary 100.0% (100.0%, 100.0%) vs. 100.0% (100.0%, 100.0%), P>0.05; left coronary 100.0% (95.9%, 100.0%) vs. 100.0% (100.0%, 100.0%), P>0.05). While the saline group reached a comparable CIF% to the contrast group with right coronary arteries (100.0% (97.6%, 100.0%) vs. 100.0% (95.9%, 100.0%), P>0.05) but showed a significantly lower CIF% with left coronary arteries (84.9% (75.9%, 93.4%) vs. 100.0% (100.0%, 100.0%), P<0.05). For the average diameter of the coronary lumen, there was no statistically significant difference between the mixed medium group and the saline group compared to the contrast group with both right and left coronary arteries (P>0.05). Conclusions: A 1∶1 heparinized saline and contrast mixture can serve as a substitute flushing medium for OCT examination during PCI procedure. Pure saline can also yield good results in OCT examination of the right coronary artery, and both alternatives are safe for use as flushing medium in OCT imaging.


Subject(s)
Coronary Artery Disease , Percutaneous Coronary Intervention , Humans , Male , Middle Aged , Aged , Tomography, Optical Coherence/methods , Percutaneous Coronary Intervention/methods , Coronary Angiography , Prospective Studies , Stents , Coronary Vessels/diagnostic imaging , Coronary Vessels/pathology , Treatment Outcome , Coronary Artery Disease/pathology , Predictive Value of Tests
14.
Theranostics ; 14(3): 1241-1259, 2024.
Article in English | MEDLINE | ID: mdl-38323308

ABSTRACT

Rationale: The transition from acute inflammation to fibrosis following myocardial ischemia‒reperfusion (MIR) significantly affects prognosis. Macrophages play a pivotal role in inflammatory damage and repair after MIR. However, the heterogeneity and transformation mechanisms of macrophages during this transition are not well understood. Methods: In this study, we used single-cell RNA sequencing (scRNA-seq) and mass cytometry to examine murine monocyte-derived macrophages after MIR to investigate macrophage subtypes and their roles in the MIR process. S100a9-/- mice were used to establish MIR model to clarify the mechanism of alleviating inflammation and fibrosis after MIR. Reinfusion of bone marrow-derived macrophages (BMDMs) after macrophage depletion (MD) in mice subjected to MIR were performed to further examine the role of S100a9hi macrophages in MIR. Results: We identified a unique subtype of S100a9hi macrophages that originate from monocytes and are involved in acute inflammation and fibrosis. These S100a9hi macrophages infiltrate the heart as early as 2 h post-reperfusion and activate the Myd88/NFκB/NLRP3 signaling pathway, amplifying inflammatory responses. As the tissue environment shifts from proinflammatory to reparative, S100a9 activates transforming growth factor-ß (Tgf-ß)/p-smad3 signaling. This activation not only induces the transformation of myocardial fibroblasts to myofibroblasts but also promotes fibrosis via the macrophage-to-myofibroblast transition (MMT). Targeting S100a9 with a specific inhibitor could effectively mitigate acute inflammatory damage and halt the progression of fibrosis, including MMT. Conclusion: S100a9hi macrophages are a promising therapeutic target for managing the transition from inflammation to fibrosis after MIR.


Subject(s)
Coronary Artery Disease , Myocardial Reperfusion Injury , Mice , Animals , Macrophages/metabolism , Myocardial Reperfusion Injury/pathology , Fibrosis , Inflammation/metabolism , Coronary Artery Disease/pathology , Ischemia/pathology , Reperfusion , Sequence Analysis, RNA , Mice, Inbred C57BL
15.
Int J Mol Sci ; 25(3)2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38338972

ABSTRACT

Computed tomography angiography (CTA) has validated the use of pericoronary adipose tissue (PCAT) attenuation as a credible indicator of coronary inflammation, playing a crucial role in coronary artery disease (CAD). This study aimed to evaluate the long-term effects of high-dose statins on PCAT attenuation at coronary lesion sites and changes in plaque distribution. Our prospective observational study included 52 patients (mean age 60.43) with chest pain, a low-to-intermediate likelihood of CAD, who had documented atheromatous plaque through CTA, performed approximately 1 year and 3 years after inclusion. We utilized the advanced features of the CaRi-Heart® and syngo.via Frontier® systems to assess coronary plaques and changes in PCAT attenuation. The investigation of changes in plaque morphology revealed significant alterations. Notably, in mixed plaques, calcified portions increased (p < 0.0001), while non-calcified plaque volume (NCPV) decreased (p = 0.0209). PCAT attenuation generally decreased after one year and remained low, indicating reduced inflammation in the following arteries: left anterior descending artery (LAD) (p = 0.0142), left circumflex artery (LCX) (p = 0.0513), and right coronary artery (RCA) (p = 0.1249). The CaRi-Heart® risk also decreased significantly (p = 0.0041). Linear regression analysis demonstrated a correlation between increased PCAT attenuation and higher volumes of NCPV (p < 0.0001, r = 0.3032) and lipid-rich plaque volume (p < 0.0001, r = 0.3281). Our study provides evidence that high-dose statin therapy significantly reduces CAD risk factors, inflammation, and plaque vulnerability, as evidenced by the notable decrease in PCAT attenuation, a critical indicator of plaque progression.


Subject(s)
Coronary Artery Disease , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Plaque, Atherosclerotic , Humans , Middle Aged , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/drug therapy , Plaque, Atherosclerotic/pathology , Computed Tomography Angiography/methods , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Follow-Up Studies , Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/drug therapy , Coronary Artery Disease/pathology , Inflammation/drug therapy , Inflammation/pathology , Coronary Vessels/diagnostic imaging , Coronary Vessels/pathology , Adipose Tissue
16.
Int J Cardiovasc Imaging ; 40(4): 699-708, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38416297

ABSTRACT

The morphological characteristics of in-stent restenosis (ISR) in relation to varying degrees of area stenosis have not been comprehensively examined. This study aimed to explore the tissue characteristics of patients experiencing ISR with different degrees of area stenosis through the utilization of optical coherence tomography (OCT). In total, 230 patients with ISR who underwent OCT were divided into the following three groups: area stenosis (AS) < 70% (n = 26); 70-80% (n = 119) and AS ≥ 80% (n = 85). Among the 230 patients, the clinical presentation as stable angina was 61.5% in AS < 70%, followed by 47.2% in 70% < AS ≤ 80%, and 31.8% in AS ≥ 80% (P = 0.010). The OCT findings showed that heterogeneous neointima, ISNA, LRP, neointima rupture, TCFA-like pattern, macrophage infiltration, red and white thrombus was more common with AS increased. Ordinal logistic regression analysis showed that higher AS was associated with previous dyslipidemia (odds ratio [OR], 4.754; 95% confidence interval [CI], 1.419-15.927, P = 0.011), neointimal rupture (OR: 3.640; 95% CI, 1.169-11.325, P = 0.026), red thrombus (OR: 4.482; 95% CI, 1.269-15.816, P = 0.020) and white thrombus (OR: 5.259; 95% CI, 1.660-16.659, P = 0.005). Patients with higher degrees of area stenosis in the context of ISR exhibited a greater number of discernible morphological characteristics as identified through OCT analysis. Furthermore, previous dyslipidemia, neointimal rupture, white thrombus and red thrombus were highly associated with and the progression of ISR lesions.


Subject(s)
Coronary Restenosis , Coronary Vessels , Neointima , Percutaneous Coronary Intervention , Predictive Value of Tests , Severity of Illness Index , Stents , Tomography, Optical Coherence , Humans , Male , Female , Coronary Restenosis/diagnostic imaging , Coronary Restenosis/etiology , Coronary Restenosis/pathology , Middle Aged , Aged , Coronary Vessels/diagnostic imaging , Coronary Vessels/pathology , Percutaneous Coronary Intervention/instrumentation , Percutaneous Coronary Intervention/adverse effects , Risk Factors , Treatment Outcome , Retrospective Studies , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Coronary Artery Disease/pathology , Coronary Stenosis/diagnostic imaging , Coronary Stenosis/pathology , Coronary Stenosis/therapy , Rupture, Spontaneous
17.
Sci Rep ; 14(1): 4412, 2024 02 22.
Article in English | MEDLINE | ID: mdl-38388639

ABSTRACT

Drug-coated balloon (DCB) angioplasty is one of the potential approaches to alleviating in-stent restenosis and treating peripheral artery disease. An in-silico model has been developed for sirolimus drug eluted from an inflated balloon in a patient-specific arterial cross-section consisting of fibrous tissue, fibrofatty tissue, dense calcium, necrotic core, and healthy tissue. The convection-diffusion-reaction equation represents the transport of drug, while drug binding, both specific and non-specific, can be modelled as a reaction process. The Brinkman equations describe the interstitial flow in porous tissue. An image processing technique is leveraged for reconstructing the computational domain. The Marker and Cell, and Immersed Boundary Methods are used to solve the set of governing equations. The no-flux interface condition and convection do amplify the tissue content, and the regions of dense calcium and necrotic core limited to or extremely close to the interface pose a clinical threat to DCB therapy. Simulations predict the effects of the positioning and clustering of plaque components in the domain. This study demands extensive intravascular ultrasound-derived virtual histology (VH-IVUS) imaging to understand the plaque morphology and determine the relative positions of different plaque compositions about the lumen-tissue interface, which have a significant impact on arterial pharmacokinetics.


Subject(s)
Angioplasty, Balloon, Coronary , Angioplasty, Balloon , Coronary Artery Disease , Plaque, Atherosclerotic , Humans , Calcium , Plaque, Atherosclerotic/therapy , Arteries/pathology , Necrosis , Ultrasonography, Interventional/methods , Coronary Artery Disease/pathology
18.
Nature ; 626(8000): 799-807, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38326615

ABSTRACT

Linking variants from genome-wide association studies (GWAS) to underlying mechanisms of disease remains a challenge1-3. For some diseases, a successful strategy has been to look for cases in which multiple GWAS loci contain genes that act in the same biological pathway1-6. However, our knowledge of which genes act in which pathways is incomplete, particularly for cell-type-specific pathways or understudied genes. Here we introduce a method to connect GWAS variants to functions. This method links variants to genes using epigenomics data, links genes to pathways de novo using Perturb-seq and integrates these data to identify convergence of GWAS loci onto pathways. We apply this approach to study the role of endothelial cells in genetic risk for coronary artery disease (CAD), and discover 43 CAD GWAS signals that converge on the cerebral cavernous malformation (CCM) signalling pathway. Two regulators of this pathway, CCM2 and TLNRD1, are each linked to a CAD risk variant, regulate other CAD risk genes and affect atheroprotective processes in endothelial cells. These results suggest a model whereby CAD risk is driven in part by the convergence of causal genes onto a particular transcriptional pathway in endothelial cells. They highlight shared genes between common and rare vascular diseases (CAD and CCM), and identify TLNRD1 as a new, previously uncharacterized member of the CCM signalling pathway. This approach will be widely useful for linking variants to functions for other common polygenic diseases.


Subject(s)
Coronary Artery Disease , Endothelial Cells , Genome-Wide Association Study , Hemangioma, Cavernous, Central Nervous System , Humans , Coronary Artery Disease/genetics , Coronary Artery Disease/pathology , Endothelial Cells/metabolism , Endothelial Cells/pathology , Genetic Predisposition to Disease/genetics , Hemangioma, Cavernous, Central Nervous System/genetics , Hemangioma, Cavernous, Central Nervous System/pathology , Polymorphism, Single Nucleotide , Epigenomics , Signal Transduction/genetics , Multifactorial Inheritance
19.
Circulation ; 149(22): 1752-1769, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38348663

ABSTRACT

BACKGROUND: Vascular calcification, which is characterized by calcium deposition in arterial walls and the osteochondrogenic differentiation of vascular smooth muscle cells, is an actively regulated process that involves complex mechanisms. Vascular calcification is associated with increased cardiovascular adverse events. The role of 4-hydroxynonenal (4-HNE), which is the most abundant stable product of lipid peroxidation, in vascular calcification has been poorly investigated. METHODS: Serum was collected from patients with chronic kidney disease and controls, and the levels of 4-HNE and 8-iso-prostaglandin F2α were measured. Sections of coronary atherosclerotic plaques from donors were immunostained to analyze calcium deposition and 4-HNE. A total of 658 patients with coronary artery disease who received coronary computed tomography angiography were recruited to analyze the relationship between coronary calcification and the rs671 mutation in aldehyde dehydrogenase 2 (ALDH2). ALDH2 knockout (ALDH2-/-) mice, smooth muscle cell-specific ALDH2 knockout mice, ALDH2 transgenic mice, and their controls were used to establish vascular calcification models. Primary mouse aortic smooth muscle cells and human aortic smooth muscle cells were exposed to medium containing ß-glycerophosphate and CaCl2 to investigate cell calcification and the underlying molecular mechanisms. RESULTS: Elevated 4-HNE levels were observed in the serum of patients with chronic kidney disease and model mice and were detected in calcified artery sections by immunostaining. ALDH2 knockout or smooth muscle cell-specific ALDH2 knockout accelerated the development of vascular calcification in model mice, whereas overexpression or activation prevented mouse vascular calcification and the osteochondrogenic differentiation of vascular smooth muscle cells. In patients with coronary artery disease, patients with ALDH2 rs671 gene mutation developed more severe coronary calcification. 4-HNE promoted calcification of both mouse aortic smooth muscle cells and human aortic smooth muscle cells and their osteochondrogenic differentiation in vitro. 4-HNE increased the level of Runx2 (runt-related transcription factor-2), and the effect of 4-HNE on promoting vascular smooth muscle cell calcification was ablated when Runx2 was knocked down. Mutation of Runx2 at lysine 176 reduced its carbonylation and eliminated the 4-HNE-induced upregulation of Runx2. CONCLUSIONS: Our results suggest that 4-HNE increases Runx2 stabilization by directly carbonylating its K176 site and promotes vascular calcification. ALDH2 might be a potential target for the treatment of vascular calcification.


Subject(s)
Aldehyde Dehydrogenase, Mitochondrial , Aldehydes , Core Binding Factor Alpha 1 Subunit , Mice, Knockout , Myocytes, Smooth Muscle , Vascular Calcification , Animals , Aldehydes/metabolism , Vascular Calcification/metabolism , Vascular Calcification/genetics , Vascular Calcification/pathology , Humans , Core Binding Factor Alpha 1 Subunit/metabolism , Core Binding Factor Alpha 1 Subunit/genetics , Aldehyde Dehydrogenase, Mitochondrial/genetics , Aldehyde Dehydrogenase, Mitochondrial/metabolism , Mice , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/pathology , Myocytes, Smooth Muscle/drug effects , Male , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Female , Middle Aged , Coronary Artery Disease/metabolism , Coronary Artery Disease/genetics , Coronary Artery Disease/pathology , Cells, Cultured , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/genetics , Renal Insufficiency, Chronic/pathology , Aged
20.
J Cardiovasc Magn Reson ; 26(1): 100999, 2024.
Article in English | MEDLINE | ID: mdl-38237903

ABSTRACT

BACKGROUND: High-intensity plaque (HIP) on magnetic resonance imaging (MRI) has been documented as a powerful predictor of periprocedural myocardial injury (PMI) following percutaneous coronary intervention (PCI). Despite the recent proposal of three-dimensional HIP quantification to enhance the predictive capability, the conventional pulse sequence, which necessitates the separate acquisition of anatomical reference images, hinders accurate three-dimensional segmentation along the coronary vasculature. Coronary atherosclerosis T1-weighted characterization (CATCH) enables the simultaneous acquisition of inherently coregistered dark-blood plaque and bright-blood coronary artery images. We aimed to develop a novel HIP quantification approach using CATCH and to ascertain its superior predictive performance compared to the conventional two-dimensional assessment based on plaque-to-myocardium signal intensity ratio (PMR). METHODS: In this prospective study, CATCH MRI was conducted before elective stent implantation in 137 lesions from 125 patients. On CATCH images, dedicated software automatically generated tubular three-dimensional volumes of interest on the dark-blood plaque images along the coronary vasculature, based on the precisely matched bright-blood coronary artery images, and subsequently computed PMR and HIP volume (HIPvol). Specifically, HIPvol was calculated as the volume of voxels with signal intensity exceeding that of the myocardium, weighted by their respective signal intensities. PMI was defined as post-PCI cardiac troponin-T > 5 × the upper reference limit. RESULTS: The entire analysis process was completed within 3 min per lesion. PMI occurred in 44 lesions. Based on the receiver operating characteristic curve analysis, HIPvol outperformed PMR for predicting PMI (C-statistics, 0.870 [95% CI, 0.805-0.936] vs. 0.787 [95% CI, 0.706-0.868]; p = 0.001). This result was primarily driven by the higher sensitivity HIPvol offered: 0.886 (95% CI, 0.754-0.962) vs. 0.750 for PMR (95% CI, 0.597-0.868; p = 0.034). Multivariable analysis identified HIPvol as an independent predictor of PMI (odds ratio, 1.15 per 10-µL increase; 95% CI, 1.01-1.30, p = 0.035). CONCLUSIONS: Our semi-automated method of analyzing coronary plaque using CATCH MRI provided rapid HIP quantification. Three-dimensional assessment using this approach had a better ability to predict PMI than conventional two-dimensional assessment.


Subject(s)
Coronary Artery Disease , Coronary Vessels , Image Interpretation, Computer-Assisted , Imaging, Three-Dimensional , Percutaneous Coronary Intervention , Plaque, Atherosclerotic , Predictive Value of Tests , Humans , Male , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/pathology , Prospective Studies , Female , Middle Aged , Aged , Percutaneous Coronary Intervention/adverse effects , Coronary Vessels/diagnostic imaging , Coronary Vessels/pathology , Risk Factors , Treatment Outcome , Stents , Area Under Curve , ROC Curve , Magnetic Resonance Imaging , Reproducibility of Results
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