Electrochemical impedance spectroscopy unmasks high-risk atherosclerotic features in human coronary artery disease.

Coronary plaque rupture remains the prominent mechanism of myocardial infarction. Accurate identification of rupture-prone plaque may improve clinical management. This study assessed the discriminatory performance of electrochemical impedance spectroscopy (EIS) in human cardiac explants to detect high-risk atherosclerotic features that portend rupture risk. In this single-center, prospective study, n = 26 cardiac explants were collected for EIS interrogation of the three major coronary arteries. Vessels in which advancement of the EIS catheter without iatrogenic plaque disruption was rendered impossible were not assessed. N = 61 vessels underwent EIS measurement and histological analyses. Plaques were dichotomized according to previously established high rupture-risk parameter thresholds. Diagnostic performance was determined via receiver operating characteristic areas-under-the-curve (AUC). Necrotic cores were identified in n = 19 vessels (median area 1.53 mm2) with a median fibrous cap thickness of 62 µm. Impedance was significantly greater in plaques with necrotic core area ≥1.75 mm2 versus <1.75 mm2 (19.8 ± 4.4 kΩ vs. 7.2 ± 1.0 kΩ, p = .019), fibrous cap thickness ≤65 µm versus >65 µm (19.1 ± 3.5 kΩ vs. 6.5 ± 0.9 kΩ, p = .004), and ≥20 macrophages per 0.3 mm-diameter high-power field (HPF) versus <20 macrophages per HPF (19.8 ± 4.1 kΩ vs. 10.2 ± 0.9 kΩ, p = .002). Impedance identified necrotic core area ≥1.75 mm2, fibrous cap thickness ≤65 µm, and ≥20 macrophages per HPF with AUCs of 0.889 (95% CI: 0.716-1.000) (p = .013), 0.852 (0.646-1.000) (p = .025), and 0.835 (0.577-1.000) (p = .028), respectively. Further, phase delay discriminated severe stenosis (≥70%) with an AUC of 0.767 (0.573-0.962) (p = .035). EIS discriminates high-risk atherosclerotic features that portend plaque rupture in human coronary artery disease and may serve as a complementary modality for angiography-guided atherosclerosis evaluation.

Causal Association of Golgi Protein 73 With Coronary Artery Disease: Evidence from Proteomics and Mendelian Randomization.

Background: Identification of the unknown pathogenic factor driving atherosclerosis not only enhances the development of disease biomarkers but also facilitates the discovery of new therapeutic targets, thus contributing to the improved management of coronary artery disease (CAD). We aimed to identify causative protein biomarkers in CAD etiology based on proteomics and 2-sample Mendelian randomization (MR) design. Methods: Serum samples from 33 first-onset CAD patients and 31 non-CAD controls were collected and detected using protein array. Differentially expressed analyses were used to identify candidate proteins for causal inference. We used 2-sample MR to detect the causal associations between the candidate proteins and CAD. Network MR was performed to explore whether metabolic risk factors for CAD mediated the risk of identified protein. Vascular expression of candidate protein in situ was also detected. Results: Among the differentially expressed proteins identified utilizing proteomics, we found that circulating Golgi protein 73 (GP73) was causally associated with incident CAD and other atherosclerotic events sharing similar etiology. Network MR approach showed low-density lipoprotein cholesterol and glycated hemoglobin serve as mediators in the causal pathway, transmitting 42.1% and 8.7% effects from GP73 to CAD, respectively. Apart from the circulating form of GP73, both mouse model and human specimens imply that vascular GP73 expression was also upregulated in atherosclerotic lesions and concomitant with markers of macrophage and phenotypic switching of vascular smooth muscle cells (VSMCs). Conclusions: Our study supported GP73 as a biomarker and causative for CAD. GP73 may involve in CAD pathogenesis mainly via dyslipidemia and hyperglycemia, which may enrich the etiological information and suggest future research direction on CAD.

[Effects of Non-Pharmacological Interventions on Major Adverse Cardiac Events in Patients Underwent Percutaneous Coronary Intervention: Systematic Review and Meta-Analysis].

PURPOSE: In this study a systematic review and meta-analysis investigated the impact of non-pharmacological interventions on major adverse cardiac events (MACE) in patients with coronary artery disease who underwent percutaneous coronary intervention (PCI). METHODS: A literature search was performed using PubMed, Cochrane Library, EMBASE, and Cumulative Index to Nursing & Allied Health Literature databases up to November 2023. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. Effect sizes and 95% confidence intervals were calculated using R software (version 4.3.2). RESULTS: Eighteen randomized studies, involving 2,898 participants, were included. Of these, 16 studies with 2,697 participants provided quantitative data. Non-pharmacological interventions (education, exercise, and comprehensive) significantly reduced the risk of angina, heart failure, myocardial infarction, restenosis, cardiovascular-related readmission, and cardiovascular-related death. The subgroup meta-analysis showed that combined interventions were effective in reducing the occurrence of myocardial infarction (MI), and individual and group-based interventions had significant effects on reducing the occurrence of MACE. In interventions lasting seven months or longer, occurrence of decreased by 0.16 times, and mortality related to cardiovascular disease decreased by 0.44 times, showing that interventions lasting seven months or more were more effective in reducing MI and cardiovascular disease-related mortality. CONCLUSION: Further investigations are required to assess the cost-effectiveness of these interventions in patients undergoing PCI and validate their short- and long-term effects. This systematic review underscores the potential of non-pharmacological interventions in decreasing the incidence of MACE and highlights the importance of continued research in this area (PROSPERO registration number: CRD42023462690).

Coronary artery calcification burden, atherogenic index of plasma, and risk of adverse cardiovascular events in the general population: evidence from a mediation analysis.

BACKGROUND: Dyslipidemia and abnormal cholesterol metabolism are closely related to coronary artery calcification (CAC) and are also critical factors in cardiovascular disease death. In recent years, the atherogenic index of plasma (AIP) has been widely used to evaluate vascular sclerosis. This study aimed to investigate the potential association of AIP between CAC and major adverse cardiovascular events (MACEs). METHODS: This study included 1,121 participants whose CACs were measured by multislice spiral CT. Participants' CAC Agatston score, CAC mass, CAC volume, and number of vessels with CACs were assessed. AIP is defined as the base 10 logarithm of the ratio of triglyceride (TG) concentration to high-density lipoprotein-cholesterol (HDL-C) concentration. We investigated the multivariate-adjusted associations between AIP, CAC, and MACEs. The mediating role of the AIP in CAC and MACEs was subsequently discussed. RESULTS: During a median follow-up of 31 months, 74 MACEs were identified. For each additional unit of log-converted CAC, the MACE risk increased by 48% (HR 1.48 [95% CI 1.32-1.65]). For each additional unit of the AIP (multiplied by 10), the MACEs risk increased by 19%. Causal mediation analysis revealed that the AIP played a partial mediating role between CAC (CAC Agatston score, CAC mass) and MACEs, and the mediating proportions were 8.16% and 16.5%, respectively. However, the mediating effect of CAC volume tended to be nonsignificant (P = 0.137). CONCLUSIONS: An increased AIP can be a risk factor for CAC and MACEs. Biomarkers based on lipid ratios are a readily available and low-cost strategy for identifying MACEs and mediating the association between CAC and MACEs. These findings provide a new perspective on CAC treatment, early diagnosis, and prevention of MACEs.

LRG1 promotes atherosclerosis by inducing macrophage M1-like polarization.

Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by the accumulation of cholesterol-rich lipoproteins in macrophages. How macrophages commit to proinflammatory polarization under atherosclerosis conditions is not clear. Report here that the level of a circulating protein, leucine-rich alpha-2 glycoprotein 1 (LRG1), is elevated in the atherosclerotic tissue and serum samples from patients with coronary artery disease (CAD). LRG1 stimulated macrophages to proinflammatory M1-like polarization through the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) pathways. The LRG1 knockout mice showed significantly delayed atherogenesis progression and reduced levels of macrophage-related proinflammatory cytokines in a high-fat diet-induced Apoe-/- mouse atherosclerosis model. An anti-LRG1 neutralizing antibody also effectively blocked LRG1-induced macrophage M1-like polarization in vitro and conferred therapeutic benefits to animals with ApoE deficiency-induced atherosclerosis. LRG1 may therefore serve as an additional biomarker for CAD and targeting LRG1 could offer a potential therapeutic strategy for CAD patients by mitigating the proinflammatory response of macrophages.

Suppression of FOXC1 induces pyroptosis of the coronary artery through activation of JAK2.

BACKGROUND AND AIMS: Janus kinase 2 (JAK2) triggers endothelial pyroptosis and is associated with a multitude of pathological cardiovascular manifestations, including atherosclerosis. However, the associated transcriptional regulatory mechanisms remain unclear. In this study, we investigated a novel transcriptional regulator upstream of JAK2. METHODS: We validated the binding and regulation of Forkhead box C1 (FOXC1) and JAK2 using chromatin immunoprecipitation and luciferase reporter assays. Immunofluorescence was used to detect protein localization in cells and tissues. Immunohistochemistry, hematoxylin-eosin (HE), Masson's trichrome, and Oil Red O staining were used to identify tissue lesions. Transcriptional functions were investigated using in vitro and in vivo coronary artery disease (CAD) atherosclerosis models. RESULTS: The mRNA levels of JAK2 were considerably higher in both the cardiac tissues of mice and the peripheral blood of patients with CAD than in equivalent controls. JAK2 expression increased markedly in the coronary arteries of ApoeKO mice, whereas FOXC1 expression exhibited a decreasing trend. In vitro, FOXC1 bound to the JAK2 promoter region and inversely regulated the expression of JAK2. Mechanistic studies have revealed that the FOXC1-JAK2 pathway regulates pyroptosis and participates in the pathogenesis of human coronary artery endothelial cells (HCAECs). In vivo, the suppression of FOXC1 was confirmed to stimulate the levels of JAK2 and pyroptosis, contributing to the pathological progression of aortic and coronary artery damage. CONCLUSIONS: We established the FOXC1-JAK2 regulatory pathway and verified its reverse-regulatory function in CAD pyroptosis. Our data emphasizes that FOXC1 is critical for the treatment of pyroptosis-induced injury in patients with CAD.

Association of remnant cholesterol with coronary artery ectasia: a cross-sectional study.

OBJECTIVE: Coronary artery ectasia (CAE) is a condition characterized by the localized or widespread dilation of one or more coronary arteries. The majority of CAE patients do not present with clinical symptoms, and the exact cause of CAE remains unclear. Therefore, a retrospective analysis was conducted to explore the potential causes of CAE. METHODS: This study was a retrospective analysis of patients who underwent coronary angiography at Guangdong Provincial People's Hospital between January 2017 and July 2022, of whom 679 patients were ultimately enrolled in the study. Among them, 260 patients were diagnosed with CAE, whereas 419 patients with normal coronary results composed the control group. Remnant cholesterol (RC) was calculated as total cholesterol (TC) minus high-density lipoprotein cholesterol (HDL-C) minus low-density lipoprotein cholesterol (LDL-C). The association between RC levels and the risk of CAE was assessed via multivariable logistic models. RESULTS: Out of the 679 patients who participated in this study, with an average age of 59.9 years, 38.3% were diagnosed with CAE. Patients with CAE had higher RC levels than did those without CAE (P = 0.001). A significant positive association was observed between RC levels and the risk of CAE, with a multivariable adjusted odds ratio (OR) of 1.950 (95% confidence interval [CI]: 1.163-3.270). There was a significant positive association between RC levels and the risk of CAE in both single-vessel and multivessel dilation cases, as well as in isolated CAE and dilation secondary to coronary atherosclerosis. According to the subgroup analyses, RC levels were positively associated with the risk of CAE in participants with hypertension (OR, 1.065; 95% CI, 1.034-1.098). CONCLUSION: RC levels are positively correlated with CAE, implying that a focus on RC could be beneficial in CAE research.

Research Progress on the Pathogenesis and Treatment of Neoatherosclerosis.

Neoatherosclerosis (NA) within stents has become an important clinical problem after coronary artery stent implantation. In-stent restenosis and in-stent thrombosis are the two major complications following coronary stent placement and seriously affect patient prognosis. As the common pathological basis of these two complications, NA plaques, unlike native atherosclerotic plaques, often grow around residual oxidized lipids and stent struts. The main components are foam cells formed by vascular smooth muscle cells (VSMCs) engulfing oxidized lipids at lipid residue sites. Current research mainly focuses on optical coherence tomography (OCT) and intravascular ultrasound (IVUS), but the specific pathogenesis of NA is still unclear. A thorough understanding of the pathogenesis and pathological features of NA provides a theoretical basis for clinical treatment. This article reviews the previous research of our research group and the current situation of domestic and foreign research.

Aortic aneurysms in patients with atherosclerotic coronary artery disease in the southwestern region of Romania - clinical and histopathological study.

An aneurysm is defined as a dilation of the arterial wall with a diameter exceeding 1.5 times the normal diameter of the vessel concerned. Aortic aneurysms (AAs) can develop at any level but are mostly found at the abdominal and infrarenal levels and extend to the iliac arteries. AAs are usually asymptomatic and are most often discovered incidentally during various imaging investigations for other conditions. Rupture of an AA is usually dramatic, being one of the causes of sudden cardiac death. Surgical treatment and, more recently, endovascular treatment are the only effective methods of AA repair. In this study, we screened for the diagnosis of AAs in patients with stable exertional angina who had indications for coronary angiography. The study was carried out in the period 2021-2023 in the Institute of Cardiovascular Diseases Timisoara, Romania. Of the 2458 patients with exertional angina who required coronary angiography, a number of 1844 (75%) patients had at least one stenotic atheromatous plaque, and of these 312 patients had AAs, of which 173 at the level of the abdominal aorta.

Improved Detection of Small and Low-Density Plaques in Virtual Noncontrast Imaging-based Calcium Scoring at Photon-Counting Detector CT.

Purpose To investigate the impact of plaque size and density on virtual noncontrast (VNC)-based coronary artery calcium scoring (CACS) using photon-counting detector CT and to provide safety net reconstructions for improved detection of subtle plaques in patients whose VNC-based CACS would otherwise be erroneously zero when compared with true noncontrast (TNC)-based CACS. Materials and Methods In this prospective study, CACS was evaluated in a phantom containing calcifications with different diameters (5, 3, and 1 mm) and densities (800, 400, and 200 mg/cm3) and in participants who underwent TNC and contrast-enhanced cardiac photon-counting detector CT (July 2021-March 2022). VNC images were reconstructed at different virtual monoenergetic imaging (55-80 keV) and quantum iterative reconstruction (QIR) levels (QIR,1-4). TNC scans at 70 keV with QIR off served as the reference standard. In vitro CACS was analyzed using standard settings (3.0-mm sections, kernel Qr36, 130-HU threshold). Calcification detectability and CACS of small and low-density plaques were also evaluated using 1.0-mm sections, kernel Qr44, and 120- or 110-HU thresholds. Safety net reconstructions were defined based on background Agatston scores and evaluated in vivo in TNC plaques initially nondetectable using standard VNC reconstructions. Results The in vivo cohort included 63 participants (57.8 years ± 15.5 [SD]; 37 [59%] male, 26 [41%] female). Correlation and agreement between standard CACSVNC and CACSTNC were higher in large- and medium-sized and high- and medium-density than in low-density plaques (in vitro: intraclass correlation coefficient [ICC] ≥ 0.90; r > 0.9 vs ICC = 0.20-0.48; r = 0.5-0.6). Small plaques were not detectable using standard VNC reconstructions. Calcification detectability was highest using 1.0-mm sections, kernel Qr44, 120- and 110-HU thresholds, and QIR level of 2 or less VNC reconstructions. Compared with standard VNC, using safety net reconstructions (55 keV, QIR 2, 110-HU threshold) for in vivo subtle plaque detection led to higher detection (increased by 89% [50 of 56]) and improved correlation and agreement of CACSVNC with CACSTNC (in vivo: ICC = 0.51-0.61; r = 0.6). Conclusion Compared with TNC-based calcium scoring, VNC-based calcium scoring was limited for small and low-density plaques but improved using safety net reconstructions, which may be particularly useful in patients with low calcium scores who would otherwise be treated based on potentially false-negative results. Keywords: Coronary Artery Calcium CT, Photon-Counting Detector CT, Virtual Noncontrast, Plaque Size, Plaque Density Supplemental material is available for this article. © RSNA, 2024.

The uric acid/HDL-C ratio may predict significant coronary stenosis in moderate left main coronary artery lesions: an intravascular ultrasonography study.

BACKGROUND: There may be severe difficulties in determining the severity of LMCA (left main coronary artery) lesions. The use of intravascular ultrasound (IVUS) facilitates decisions about lesion severity in these patients. The aim of this study was to investigate the relationship between the UHR (uric acid to HDL-C ratio) and lesion severity in patients who underwent LMCA IVUS. METHODS: This study included 205 patients with ICS (intermediate coronary stenosis) in the LMCA who underwent IVUS. In the IVUS measurements of these patients, the plaque burden (PB) and the minimal lumen area (MLA) showing lesion severity were measured. RESULTS: The patients were separated into two groups according to plaque burden (< 65% and ≥ 65%). The UHR was significantly greater in the high plaque burden group (479.5 vs. 428.6, P = 0.001). When the patients were separated into two groups according to the MLA (< 6mm2 and ≥ 6mm2), the UHR was determined to be significantly greater in the group with low MLA (476.8 vs. 414.9, P < 0.001). In the ROC analysis performed according to the MLA and plaque burden values, the UHR cutoff value of 450 was found to have similar sensitivity and the same specificity for both parameters. CONCLUSIONS: The results of this study suggested that there is a relationship between UHR and MLA < 6mm2 and plaque burden ≥ 65%, which are independently evaluated as critical in IVUS, and this could predict anatomically significant lesions in patients with a moderate degree of LMCA stricture.

Correlation between controlled attenuation parameter values with SYNTAX score in patients with significant coronary artery disease.

Non-alcoholic fatty liver disease (NAFLD) is an emerging cause of chronic liver disease, with coronary artery disease (CAD) as the main cause of death in NAFLD patients. However, correlation between the severity of liver steatosis and coronary atherosclerosis is yet to be understood. Here we aim to explore the correlation between controlled attenuation parameter (CAP) values and SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score in adult patients with significant CAD, defined as ≥ 50% stenosis of the left main coronary artery, or ≥ 70% stenosis of the other major coronary arteries. A cross-sectional study was conducted on 124 adult patients with significant CAD who underwent coronary angiography. Transient elastography with CAP was used to assess liver steatosis severity, resulting in a mean CAP value of 256.5 ± 47.3 dB/m, with 52.5% subjects had significant steatosis (CAP value of ≥ 248 dB/m). Median SYNTAX score was 22. A statistically significant correlation was observed between CAP value and SYNTAX score (r = 0.245, p < 0.0001). The correlation was more pronounced in patients with prior history of PCI (r = 0.389, p = 0.037). Patients with high-risk SYNTAX score (> 32) had the highest CAP value (285.4 ± 42.6 dB/m), and it was significantly higher than those with low-risk SYNTAX score (0-22), with a mean difference of 38.76 dB/m (p = 0.006). Patients with significant liver steatosis should undergo periodic CAD assessment and lifestyle modification, especially those with severe liver steatosis.

Diagnostic values of inferior Q-waves for myocardial scar identification detected by 3.0 T cardiac MRI.

While Q-waves in inferior leads, particularly lead III, can be regarded as a minor abnormality, it can also indicate the presence of myocardial scar. This study assessed the diagnostic value of pathologic inferior Q-waves (lead II, III, aVF) for detecting ischemic scars using a high-resolution 3.0 T cardiac magnetic resonance (CMR). We retrospectively analyzed 1692 patients with suspected or known coronary artery disease who underwent stress CMR perfusion or viability assessment. Pathologic Q-waves were defined as duration of ≥ 30 ms and depth of ≥ 1 mm or QS-complex. Eleven models were created to evaluate the presence of Q-waves in different combinations of inferior leads. Of the 1692 patients, 436 (25.8%) had pathologic Q-waves. Models with Q-waves in leads II + aVF (model 7) and II + III + aVF (model 9) showed high specificity (100% and 99.6%), positive predictive value (PPV) (80.0% and 86.7%), and negative predictive value (NPV) (82.6% and 84.3%) but low sensitivity (1.3% and 13.1%). Other models also maintained high specificity and NPV but poor sensitivity and PPV. Notably, 21% of patients with an isolated pathologic Q-wave in lead III (model 4) exhibited scars. These findings highlight the need for careful clinical assessment when pathologic Q-waves are present.

Differential responses to thrombospondin-1 and PDGF-BB in smooth muscle cells from atherosclerotic coronary arteries and internal thoracic arteries.

Atherosclerosis is rare in internal thoracic arteries (ITA) even in patients with severe atherosclerotic coronary artery (ACA) disease. To explore cellular differences, ITA SMC from 3 distinct donors and ACA SMC from 3 distinct donors were grown to sub-confluence and growth arrested for 48 h. Proliferation and thrombospondin-1 (TSP1) production were determined using standard techniques. ITA SMC were larger, grew more slowly and survived more passages than ACA SMC. ACA SMC had a more pronounced proliferative response to 10% serum than ITA SMC. Both ACA SMC and ITA SMC proliferated in response to exogenous TSP1 (12.5 µg/ml and 25 µg/ml) and platelet derived growth factor-BB (PDGF-BB; 20 ng/ml) but TSP1- and PDGF-BB-induced proliferation were partially inhibited by anti-TSP1 antibody A4.1, microRNA-21(miR-21)-3p inhibitors and miR-21-5p inhibitors in each of the 3 ACA SMC lines, but not in any of the ITA SMC lines. PDGF-BB stimulated TSP1 production in ACA SMC but not in ITA SMC but there was no increase in TSP1 levels in conditioned media in either SMC type. In summary, there are significant differences in morphology, proliferative capacity and in responses to TSP1 and PDGF-BB in SMC derived from ITA compared to SMC derived from ACA.

SREBP-1-mediated lipogenesis confers resistance to ferroptosis and improves endothelial injury.

Atherosclerosis refers to a disease characterized by the formation of lipid plaque deposits within arterial walls, leading to reduced blood flow or blockage of blood outflow. The process of endothelial injury induced by oxidized low-density lipoprotein (ox-LDL) is considered the initial stage of atherosclerosis. Ferroptosis is a form of iron-dependent, non-apoptotic cell death, and current research suggests its association with coronary artery disease (CAD). In this study, we observed a correlation between reduced expression of SREBP-1 and the occurrence of stable CAD. Additionally, during the process of endothelial injury induced by ox-LDL, we also noted decreased expression of the SREBP-1/SCD1/FADS2 and involvement in the ferroptosis process. Mechanistically, ox-LDL induced endothelial injury by inhibiting the lipid biosynthesis process mediated by the SREBP-1/SCD1/FADS2, thereby inducing lipid peroxidation and ferroptosis. On the contrary, overexpression of SREBP-1 or supplementation with monounsaturated fatty acids counteracted iron accumulation, mitochondrial damage, and lipid peroxidation-induced ferroptosis, thereby improving endothelial injury. Our study indicated that the decreased expression of peripheral blood SREBP-1 mRNA is an independent risk factor for stable CAD. Furthermore, in endothelial cells, the lipid biosynthesis process mediated by SREBP-1 could ameliorate endothelial injury by resisting ferroptosis. The study has been registered with the Chinese Clinical Trial Registry, which serves as a primary registry in the World Health Organization International Clinical Trials Registry Platform (ChiCTR2300074315, August 3rd, 2023).

Invasive Assessment of Coronary Artery Disease in Clonal Hematopoiesis of Indeterminate Potential.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) occurs due to acquired mutations in bone marrow progenitor cells. CHIP confers a 2-fold risk of atherosclerotic cardiovascular disease. However, there are limited data regarding specific cardiovascular phenotypes. The purpose of this study was to define the coronary artery disease phenotype of the CHIP population-based on coronary angiography. METHODS: We recruited 1142 patients from the Vanderbilt University Medical Center cardiac catheterization laboratory and performed DNA sequencing to determine CHIP status. Multivariable logistic regression models and proportional odds models were used to assess the association between CHIP status and angiography phenotypes. RESULTS: We found that 18.4% of patients undergoing coronary angiography had a CHIP mutation. Those with CHIP had a higher risk of having obstructive left main (odds ratio, 2.44 [95% CI, 1.40-4.27]; P=0.0018) and left anterior descending (odds ratio, 1.59 [1.12-2.24]; P=0.0092) coronary artery disease compared with non-CHIP carriers. We additionally found that a specific CHIP mutation, ten eleven translocase 2 (TET2), has a larger effect size on left main stenosis compared with other CHIP mutations. CONCLUSIONS: This is the first invasive assessment of coronary artery disease in CHIP and offers a description of a specific atherosclerotic phenotype in CHIP wherein there is an increased risk of obstructive left main and left anterior descending artery stenosis, especially among TET2 mutation carriers. This serves as a basis for understanding enhanced morbidity and mortality in CHIP.

Homocysteine concentration in coronary artery disease and severity of coronary lesions.

Our previous study reckons that the impact of the rs1801133 variant of 5,10-methylenetetrahydrofolate reductase (MTHFR) on coronary artery disease (CAD) is possibly mediated by cardiometabolic disorder. This study is performed to verify this hypothesis. Four hundred and thirty CAD patients and 216 CAD-free individuals were enrolled in this case-control study. The rs1801133 variant was genotyped by PCR-RFLP. Severity of coronary lesions was evaluated by number of stenotic coronary vessels and extent of coronary stenosis. The rs1801133 T allele significantly increased homocysteine levels in patients with CAD and CAD-free individuals. Individuals with the T allele of rs1801133 had an increased risk of developing CAD. In contrast, individuals with the TT genotype of rs1801133 were at high risk of multiple vessel lesions. The carriers of CT genotype had higher levels of systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein (hs-CRP), and lower levels of apolipoprotein A1 (APOA1) than those with CC genotype in male patients with CAD. The receiver operating characteristic (ROC) curve and precision-recall (PR) curve indicated that hyperhomocysteinemia was sensitive to predict the severity of CAD. Multivariate logistic regression revealed that homocysteine, rs1801133, age, smoking, weight, body mass index (BMI), lipoprotein(a) [Lp(a)], and hs-CRP were independent risk factors for CAD. The increased risk of CAD and severity of coronary lesions associated with rs1801133 in the Chinese Han population were attributed, at least partly, to high homocysteine levels. Hyperhomocysteinemia had a high predictive value for severe CAD or multiple vessel lesions.

AIM2 inflammasome regulated by the IFN-γ/JAK2/STAT1 pathway promotes activation and pyroptosis of monocytes in Coronary Artery Disease.

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.

Sex-related differences in coronary and carotid vessel geometry, plaque composition and shear stress obtained from imaging.

Atherosclerosis manifests itself differently in men and women with respect to plaque initiation, progression and plaque composition. The observed delay in plaque progression in women is thought to be related to the hormonal status of women. Also features associated with the vulnerability of plaques to rupture seem to be less frequently present in women compared to men. Current invasive and non-invasive imaging modalities allow for visualization of plaque size, composition and high risk vulnerable plaque features. Moreover, image based modeling gives access to local shear stress and shear stress-related plaque growth. In this review, current knowledge on sex-related differences in plaque size, composition, high risk plaque features and shear stress related plaque growth in carotid and coronary arteries obtained from imaging are summarized.