The relationship between glycemic risk and longitudinal changes in total physiological atherosclerotic burden in patients with coronary artery disease.

Background: The effects of glycemic status on coronary physiology have not been well evaluated. This study aimed to investigate changes in coronary physiology by using angiographic quantitative flow ratio (QFR), and their relationships with diabetes mellitus (DM) and glycemic control status. Methods: This retrospective cohort study included 530 patients who underwent serial coronary angiography (CAG) measurements between January 2016 and December 2021 at Tongji Hospital of Tongji University. Based on baseline and follow-up angiograms, 3-vessel QFR (3V-QFR) measurements were performed. Functional progression of coronary artery disease (CAD) was defined as a change in 3V-QFR (Δ3V-QFR = 3V-QFRfollow-up - 3V-QFRbaseline) ≤-0.05. Univariable and multivariable logistic regression analyses were applied to identify the independent predictors of coronary functional progression. Subgroup analysis according to diabetic status was performed. Results: During a median interval of 12.1 (10.6, 14.3) months between the two QFR measurements, functional progression was observed in 169 (31.9%) patients. Follow-up glycosylated hemoglobin (HbA1c) was predictive of coronary functional progression with an area under the curve (AUC) of 0.599 [95% confidence interval (CI): 0.546-0.651; P<0.001] in the entire population. Additionally, the Δ3V-QFR values were significantly lower in diabetic patients with HbA1c ≥7.0% compared to those with well-controlled HbA1c or non-diabetic patients [-0.03 (-0.09, 0) vs. -0.02 (-0.05, 0.01) vs. -0.02 (-0.05, 0.02); P=0.002]. In a fully adjusted multivariable logistics analysis, higher follow-up HbA1c levels were independently associated with progression in 3V-QFR [odds ratio (OR), 1.263; 95% CI: 1.078-1.479; P=0.004]. Furthermore, this association was particularly strong in diabetic patients (OR, 1.353; 95% CI: 1.082-1.693; P=0.008) compared to patients without DM. Conclusions: Among patients with established CAD, on-treatment HbA1c levels were independently associated with progression in physiological atherosclerotic burden, especially in patients with DM.

Prognostic Implications of Changes in Total Physiological Atherosclerotic Burden in Patients With Coronary Artery Disease-A Serial QFR Study.

The association between coronary physiological progression and clinical outcomes has not been investigated. A total of 421 patients who underwent serial coronary angiography at least 6 months apart were included. Total physiological atherosclerotic burden was characterized by sum of quantitative flow ratio in 3 epicardial vessels (3V-QFR). The relationships of the 3V-QFR and its longitudinal change (△3V-QFR) with major adverse cardiovascular events (MACE) were explored. 3V-QFR values derived from follow-up angiograms were slightly lower compared with baseline (2.85 [2.77, 2.90] vs 2.86 [2.80, 2.90], P < .001). The median △3V-QFR value was -0.01 (-0.05, 0.02). The multivariable models demonstrated that follow-up 3V-QFR and △3V-QFR were independently associated with MACE (both P < .05). Patients with both low follow-up 3V-QFR (≤2.78) and low △3V-QFR (≤-0.05) presented 3 times higher risk of MACE than those without (hazard ratio: 2.953, 95% confidence interval 1.428-6.104, P = .003). Furthermore, adding patient-level 3V-QFR and △3V-QFR to clinical model significantly improved the predictability for MACE. In conclusion, total physiological atherosclerotic burden and its progression can provide incremental prognostic value over clinical characteristics, supporting the use of coronary physiology in the evaluation of disease progression and for the identification of vulnerable patients.

Species Identification of Caviar Based on Multiple DNA Barcoding.

This study aimed to explore the applicability of DNA barcoding for assessing the authenticity of caviar on the Chinese market. A set of universal COI primers and two sets of designed primers based on COI and D-loop genes were used to identify maternal species of samples from 21 batches of caviar. The results showed that the PCR products from three sets of primers had more than 98% similarity to the sequences in database. The COI gene could not distinguish sturgeons with closed genetic relationships, while D-loop gene could effectively improve the accuracy of DNA barcoding and was more suitable to the identification of interspecific sturgeon than the COI gene. The neighbor-joining dendrogram further confirmed the applicability and accuracy of COI and D-loop genes in identifying maternal relatives of caviar (Acipenser baerii/Acipenser gueldenstaedtii/Acipenser schrenckii/Huso dauricus/Huso huso). Despite the limitations of mitochondrial DNA in identifying hybrid sturgeon species, the presence of counterfeit caviar of non-sturgeon ingredients could be excluded. All the caviar samples were identified successfully as sturgeon species, but the mislabeling rate of species was 33.4%, indicating that there were illegal phenomena such as disorderly labeling, mislabeling, and adulteration on the market.

Screening of Potential Circulating Diagnostic Biomarkers and Molecular Mechanisms of Systemic Lupus Erythematosus-Related Myocardial Infarction by Integrative Analysis.

Background: The risk of acute myocardial infarction (AMI) is elevated in patients with systemic lupus erythematosus (SLE), and it is of great clinical value to identify potential molecular mechanisms and diagnostic markers of AMI associated with SLE by analyzing public database data and transcriptome sequencing data. Methods: AMI and SLE-related sequencing datasets GSE62646, GSE60993, GSE50772 and GSE81622 were downloaded from the Gene Expression Omnibus (GEO) database and divided into prediction and validation cohorts. To identify the key genes associated with AMI related to SLE, WGCNA and DEGs analysis were performed for the prediction and validation cohorts, respectively. The related signaling pathways were identified by GO/KEGG enrichment analysis. Peripheral blood mononuclear cells (PBMCs) from patients with AMI were collected for transcriptome sequencing to validate the expression of key genes in patients with AMI. Least absolute shrinkage and selection operator (LASSO) regression analysis was applied to screen diagnostic biomarkers. The diagnostic efficacy of biomarkers was validated by ROC analysis, and the CIBERSORTx platform was used to analyze the composition of immune cells in AMI and SLE. Results: A total of 108 genes closely related to AMI and SLE were identified in the prediction cohort, and GO/KEGG analysis showed significantly enriched signaling pathways. The results of differential analysis in validation cohort were consistent with them. By transcriptional sequencing of PBMCs from peripheral blood of AMI patients, combined with the results of prediction and validation cohort analysis, seven genes were finally screened out. LASSO analysis finally identifies DYSF, LRG1 and CSF3R as diagnostic biomarkers of SLE-related-AMI. CIBERSORTx analysis revealed that the biomarkers were highly correlated with neutrophils. Conclusion: Neutrophil degranulation and NETs formation play important roles in SLE-related AMI, and DYSF, LRG1 and CSF3R were identified as important diagnostic markers for the development and progression of SLE-related AMI.

Single-Cell RNA Sequencing of Peripheral Blood Mononuclear Cells From Acute Myocardial Infarction.

Background: Acute myocardial infarction (AMI) can occur in patients with atherosclerotic disease, with or without plaque rupture. Previous studies have indicated a set of immune responses to plaque rupture. However, the specific circulating immune cell subsets that mediate inflammatory plaque rupture remain elusive. Methods: Ten AMI patients were enrolled in our study (five with and five without plaque rupture; plaque characteristics were identified by optical coherence tomography). By single-cell RNA sequencing, we analyzed the transcriptomic profile of peripheral blood mononuclear cells. Results: We identified 27 cell clusters among 82,550 cells, including monocytes, T cells, NK cells, B cells, megakaryocytes, and CD34+ cells. Classical and non-classical monocytes constitute the major inflammatory cell types, and pro-inflammatory genes such as CCL5, TLR7, and CX3CR1 were significantly upregulated in patients with plaque rupture, while the neutrophil activation and degranulation genes FPR2, MMP9, and CLEC4D were significantly expressed in the intermediate monocytes derived from patients without plaque rupture. We also found that CD4+ effector T cells may contribute to plaque rupture by producing a range of cytokines and inflammatory-related chemokines, while CD8+ effector T cells express more effector molecules in patients without plaque rupture, such as GZMB, GNLY, and PRF1, which may contribute to the progress of plaque erosion. Additionally, NK and B cells played a significant role in activating inflammatory cells and promoting chemokine production in the plaque rupture. Cell-cell communication elaborated characteristics in signaling pathways dominated by inflammatory activation of classical monocytes in patients with plaque rupture. Conclusions: Our studies demonstrate that the circulating immune cells of patients with plaque rupture exhibit highly pro-inflammatory characteristics, while plaque erosion is mainly associated with intermediate monocyte amplification, neutrophil activation, and degranulation. These findings may provide novel targets for the precise treatment of patients with AMI.

miR-129-5p restores cardiac function in rats with chronic heart failure by targeting the E3 ubiquitin ligase Smurf1 and promoting PTEN expression.

Chronic heart failure (CHF) is a prevalent health concern with complex pathogenesis. This current study set out to estimate the function of the miR-129-5p/Smurf1/PTEN axis on cardiac function injury in CHF. The model of CHF in rats was established. The cardiac function indexes, myocardial tissue damage, and oxidative stress-related factors in CHF rats were evaluated after the interference of Smurf1/miR-129-5p/PTEN. The targeting relationships between miR-129-5p and Smurf1 and between PTEN and Smurf1 were verified. It was found that that after modeling, cardiac functions were impaired, heart/left ventricular/lung weight and the myocardial structure was destroyed, and the degree of fibrosis of myocardial tissue was increased. After Smurf1 knockdown, the cardiac function, myocardial structure, and oxidative stress were improved, and the fibrosis in myocardial tissue was decreased. Smurf1 was a target of miR-129-5p. miR-129-5p could annul the protective effect of Smurf1 silencing on CHF rats. Smurf1 inhibited PTEN expression by promoting PTEN ubiquitination, while miR-129-5p enhanced PTEN expression by inhibiting Smurf1. Meanwhile, overexpression of PTEN annulled the cardiac dysfunction in CHF rats induced by Smurf1. In conclusion, miR-129-5p targeted Smurf1 and repressed the ubiquitination of PTEN, and promoted PTEN expression, thus improving the cardiac function of CHF rats.

Clinical implication of quantitative flow ratio to predict clinical events after drug-coated balloon angioplasty in patients with in-stent restenosis.

BACKGROUND: The association between the quantitative flow ratio (QFR) and adverse events after drug-coated balloon (DCB) angioplasty for in-stent restenosis (ISR) lesions has not been investigated. HYPOTHESIS: Post-procedural QFR is related to adverse events in patients undergoing DCB angioplasty for ISR lesions. METHODS: This retrospective study included data from patients undergoing DCB angioplasty for drug-eluting stent (DES) ISR between January 2016 and February 2019. The QFR was measured at baseline and after DCB angioplasty. The endpoint was the vessel-oriented composite endpoint (VOCE), defined as a composite of cardiac death, vessel-related myocardial infarction, and ischemia-driven target vessel revascularization. RESULTS: Overall, 177 patients with 185 DES-ISR lesions were included. During 1-year follow-up, 27 VOCEs occurred in 26 patients. The area under curve (AUC) of the post-procedural QFR was statistically greater than that of the in-stent percent diameter stenosis (0.77, 95% confidence interval [CI] 0.67-0.87 vs. 0.64, 95% CI 0.53-0.75; p = .032). Final QFR cutoff of 0.94 has the best predictive accuracy for VOCE. A QFR > 0.94 was associated with a lower risk of VOCE compared to a QFR ≤ 0.94 (log-rank test, p < .0001). Survival analysis using the multivariable Cox model showed that a post-procedural QFR ≤ 0.94 was an independent predictor of 1-year VOCE (hazard ratio 6.53, 95% CI 2.70-15.8, p < .001). CONCLUSIONS: A lower QFR value was associated with worse clinical outcomes at 1 year after DCB angioplasty for DES-ISR.

MiR-155 acts as an inhibitory factor in atherosclerosis-associated arterial pathogenesis by down-regulating NoxA1 related signaling pathway in ApoE-/- mouse.

BACKGROUND: To investigate the protective efficacy of miR-155 on down regulating NADPH oxidase isoform subunit A1 (NoxA1) gene expression, resulting in inhibition of VSMC migration and over proliferation and thus ameliorating the progression of arterial atherosclerosis in AS mouse model. Therefore, to further explore the regulatory effect of miR-155 on neointima formation in AS and locate potential anti-atherosclerosis target. METHODS: The mouse vascular aorta smooth muscle cell (MOVAS) was cultured and transfected with recombinant Pad2YFG adenovirus fluorescent vector with miR-155 fragment into 4 groups. Western blotting and RT-PCR were performed to identify the expression of NoxA1 under different circumstances. Fluorescence microscope was applied to observe the transfection rate of miR-155 into adenovirus. Twelve-week fatty food induced atherosclerotic ApoE-/- mouse model was established as host to accept miR-155 transfected adenovirus transplantation to observe its effect on VSMC in AS progression. Carotid and thoracic artery were extracted at 1 month after dosing. Distribution of miR-155 was quantified via expression levels of protein and RNA to detect NoxA1, Nox1, p47phox and NADPH expression. Immunohistochemistry, fluorescence imaging and other methods were performed in arteries section to compare the thickness of neointima and assess the severity of AS in each group. RESULTS: Luciferase reporter gene assay showed significant expression of miR-155 in mimic group indicating that miR-155 had target binding effect with NoxA1 gene. Western blotting and RT-PCR results both showed significantly decreased NoxA1 expression in miR-155 mimic group while increased with its inhibitor. The miR-155 distribution was observed varied at 1 month after in control, miR-155 mimic and inhibitor groups. The NoxA1, NADPH, Nox1 and pp47phox protein expression in VSMC was decreased in mimic group vs control and inhibitor groups (P<0.05); no significant difference of NADPH expression was observed in all groups. The NoxA1, Nox1 and p47phox gene expression in VSMC were both found reduced compared with those of control group at week 4 (P<0.05). Immunohistochemistry staining of artery frozen sections figured out that the thickness of neointima of carotid artery in miR-155 mimic group was significantly lower vs control and inhibitor groups (P<0.01) at week 4. CONCLUSIONS: miR-155 played an important role in NoxA1-related signaling pathway. miR-155 transfection into VSMC may have anti-inflammatory regulatory effect on NoxA1 expression in vivo and resulting in amelioration of atherosclerotic lesion in AS mouse model. In summary, miR-155 specifically plays in a negative feedback loop and demonstrates a protective role during atherosclerosis-associated VSMC proliferation and neointima formation through the miR-155-NoxA1-p47phox complex signaling pathway.

Quantitative flow ratio-guided residual functional SYNTAX score for risk assessment in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention.

BACKGROUND: Functional incomplete revascularisation (IR) is associated with a higher risk of major adverse cardiac events (MACE) during long-term follow-up in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). AIMS: This study aimed to investigate the prognostic ability of quantitative flow ratio (QFR)-guided residual functional SYNTAX score (Q-rFSS) and functional IR in STEMI patients undergoing PCI. METHODS: In total, 354 consecutive STEMI patients who successfully underwent PCI were included. Q-rFSS was defined as residual SYNTAX score (rSS) measured only in vessels with QFR ≤0.8. The primary outcome was MACE (a composite of all-cause mortality, myocardial infarction, and ischaemia-driven revascularisation) at 2 years. RESULTS: At two-year follow-up, functional IR (Q-rFSS ≥1) showed significantly higher risk for MACE than functional complete revascularisation (CR) (Q-rFSS=0) (functional IR vs CR, 22.0% vs 7.4%; hazard ratio [HR] 3.21; 95% confidence interval [Cl]: 1.74 to 5.91; p<0.001). The area under the curve (AUC) of Q-rFSS (0.738, 95% CI: 0.659 to 0.817) was significantly greater than that of rSS (0.648, 95% CI: 0.547 to 0.749). The C-statistic for MACE also increased after the addition of Q-rFSS to the clinical risk factors. Q-rFSS significantly improved risk classification compared with rSS (net reclassification improvement 0.439, 95% CI: 0.201 to 0.548; p<0.001). CONCLUSIONS: Functional IR is associated with higher risk of MACE during long-term follow-up in STEMI patients undergoing PCI. Q-rFSS has a better prognostic ability for the risk of MACE.

Clinical implication of QFR in patients with ST-segment elevation myocardial infarction after drug-eluting stent implantation.

The feasibility and prognostic value of quantitative flow ratio (QFR) after percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) patients have not been assessed. The aim of this study was to investigate the prognostic utility of post-PCI QFR to predict outcomes in STEMI and determine the influence of functional results, in both culprit and nonculprit lesions, after PCI. Patients undergoing PCI of culprit lesions and receiving staged procedures of nonculprit lesions after 7 days were enrolled from 2 centers and underwent post-PCI QFR. The primary outcome was the vessel-oriented composite endpoints (VOCEs), defined as vessel-related cardiovascular death, vessel-related myocardial infarction, and target vessel revascularization. Four hundred fifteen vessels (186 culprit lesions and 219 nonculprit lesions) in 186 patients were analyzed. Measured at staged PCI, the post-PCI QFR of culprit lesions was significantly lower than that of nonculprit lesions (0.92 ± 0.10 versus 0.95 ± 0.08, p < 0.001). The multivariable model demonstrated that low post-PCI QFR was an independent predictor of 2-year VOCE (20.8% versus 5.7%; hazard ratio 2.718; 95% CI 1.347-5.486; p = 0.005). In STEMI patients with a low angiography-derived index of microcirculatory resistance (≤ 40U), a good correlation and agreement between post-PCI QFR value of culprit lesions at primary and staged procedures (r = 0.942; mean difference: - 0.0017 [- 0.074 to 0.070]) was identified. In conclusion, culprit lesions suffered from suboptimal functional results more frequently compared to nonculprit lesions after PCI in STEMI patients. Low post-PCI QFR was associated with subsequent adverse clinical outcomes. After stenting, culprit lesions may feasibly be assessed through QFR without significant microvascular dysfunction.

Association of stress hyperglycemia ratio with intracoronary thrombus burden in diabetic patients with ST-segment elevation myocardial infarction.

BACKGROUND: Large intracoronary thrombus burden is not rare during primary percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI). Stress hyperglycemia is independently associated with poor prognosis. However, the underlying relationship between stress hyperglycemia and thrombus burden remains unknown. This study aims to investigate the association of stress hyperglycemia, evaluated by the combination of acute and chronic glycemic levels, with intracoronary thrombus burden in diabetic patients with STEMI. METHODS: We enrolled 227 consecutive diabetic patients with STEMI undergoing primary PCI within 12 hours after symptom onset. Stress hyperglycemia was estimated using the stress hyperglycemia ratio (SHR), which was calculated as admission glycemia divided by estimated average glucose derived from glycosylated hemoglobin. Based on reclassified angiographic thrombolysis in myocardial infarction (TIMI) thrombus grades, patients were divided into small thrombus burden (STB) group (TIMI thrombus grades <4) and large thrombus burden (LTB) group (TIMI thrombus grades 4 or 5). RESULTS: Of the entire study population, 77 (33.9%) patients were categorized as LTB group, whereas 150 (66.1%) patients presented with STB. The mean age was 64.1 years, and 80.6% of the patients were male. The SHR levels were significantly higher in patients with LTB than in those with STB [1.31; interquartile range (IQR): 1.13-1.48 versus 1.11; IQR: 0.96-1.32; P<0.001]. The predictive performance of SHR for LTB was moderate (area under the curve: 0.669; 95% confidence interval: 0.604-0.730; P<0.001), with the best cut-off value 1.19 (sensitivity 71.4%, specificity 64.7%). The incidence of LTB with SHR ≥1.19 was significantly higher compared with SHR <1.19 (50.9% versus 18.5%; P<0.001). Based on the multivariable logistic regression analysis, the high SHR (≥1.19) was found to be an independent predictor of LTB following adjustment for baseline clinical confounders. CONCLUSIONS: A high SHR value was independently associated with large thrombus burden and has a better predictive value than glycemia at admission in diabetic patients with STEMI undergoing primary PCI. Stress hyperglycemia may play an important role on the intracoronary thrombus formation.

Optical coherence tomography and intravascular ultrasound assessment of the anatomic size and wall thickness of a muscle bridge segment.

OBJECTIVE: To use optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in assessing myocardial bridging (MB) vessel size and wall thickness. BACKGROUND: During stent implantation, MB is associated with complications, especially perforation. METHODS: OCT and IVUS were performed in 56 patients with typical angiographic "milking" from November 2016 to May 2017. The vessel area and thickness in the MB segments and adjacent proximal and distal reference segments were measured and compared with eight normal left anterior descending (LAD) segment (no atherosclerosis in a segment that was at least 20 mm long and that began ~40 mm distal to the LAD ostium). RESULTS: Compared with the reference vessel size distal to the MB segment (6.3 ± 1.8 mm2 ), the IVUS-measured size of the tunneled vessel during diastole was significantly smaller (6.0 ± 1.9 mm2 , p < 0.05) (remodeling index = 0.79 ± 0.18). The minimum intramyocardial arterial wall thickness was 0.16 ± 0.02 mm, significantly thinner than that of the mean reference (0.22 ± 0.03 mm, p < 0.001). The location of the thinnest arterial wall was in the distal and middle MB segments in 45 (80.4%) and 11 (19.6%) patients, respectively, and was not related to the degree of systolic compression or remodeling index. The walls of the middle and distal MB subsegments, but not of the proximal MB subsegment, were thinner than that of the comparison group of normal LADs. CONCLUSION: The coronary vessel involved in an MB is both smaller and thinner than that of the adjacent non-MB segment. This may explain the increased frequency and severity of coronary perforation during stent implantation.

Tryptase Promotes the Profibrotic Phenotype Transfer of Atrial Fibroblasts by PAR2 and PPARγ Pathway.

BACKGROUND: As shown in clinical and experimental studies, atrial fibrosis is an important mechanism for the occurrence and development of atrial fibrillation, the most common arrhythmia in the clinic with high disability and mortality. Some studies have shown the possible involvement of tryptase, a protease released by mast cells, in the fibrosis of heart tissues, but the effect and mechanism of tryptase on extracellular matrix (ECM) remodeling and atrial fibrosis is not clear yet. MATERIAL AND METHOD: This study evaluated the effects of tryptase on the proliferation, migration, ECM remodeling and the balance between matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) of fibroblasts by in vitro culture of atrial fibroblasts. The involvement of Protease activated receptor 2 (PAR2), platelet-derived growth factor receptor (PDGFR) or peroxisome proliferator-activated receptor (PPAR)γ were investigated with their respective antagonists. RESULTS: Tryptase significantly increased the cell proliferation, the protein levels of Collagen I, fibronectin and laminin, migration ability and MMP (-1, -2) levels of atrial fibroblasts in a time-dependent manner. The TIMP (-1, -2) levels of atrial fibroblasts were significantly decreased. PAR2 antagonist FSLLRY-NH2 or PPARγ antagonist GW9662 significantly abolished these profibrotic effects of tryptase. CONCLUSION: Tryptase may promote the profibrotic phenotype transfer of atrial fibroblasts by activating PAR2 and PPARγ. This finding may provide new strategies for the prevention of atrial fibrosis.

Qiliqiangxin Rescues Mouse Cardiac Function by Regulating AGTR1/TRPV1-Mediated Autophagy in STZ-Induced Diabetes Mellitus.

BACKGROUND/AIMS: To explore the potential role of qiliqiangxin (QLQX) A traditional Chinese medicine and the involvement of angiotensin II receptor type 1 (AGTR1) and transient receptor potential vanilloid 1 (TRPV1) in diabetic mouse cardiac function. METHODS: Intragastric QLQX was administered for 5 weeks after streptozotocin (STZ) treatment. Additionally, Intraperitoneal injections of angiotensin II (Ang II) or intragastric losartan (Los) were administered to assess the activities of AGTR1 and TRPV1. Two-dimensional echocardiography and tissue histopathology were used to assess cardiac function Western blot was used to detect the autophagic biomarkers Such as light chain 3 P62 and lysosomal-associated membrane protein 2 And transmission electron microscopy was used to count the number of autophagosomes. RESULTS: Decreased expression of TRPV1 and autophagic hallmarks and reduced numbers of autophagolysosomes as well as increased expression of angiotensin converting enzyme 1 and AGTR1 were observed in diabetic hearts. Blocking AGTR1 with Los mimicked the QLQX-mediated improvements in cardiac function Alleviated myocardial fibrosis and enabled autophagy Whereas Ang II abolished the beneficial effects of QLQX in wild type diabetic mice but not in TRPV1-/- diabetic mice. CONCLUSIONS: QLQX may improve diabetic cardiac function by regulating AGTR1/ TRPV1-mediated autophagy in STZ-induced diabetic mice.

Coronary Artery Aneurysm Differs From Coronary Artery Ectasia: Angiographic Characteristics and Cardiovascular Risk Factor Analysis in Patients Referred for Coronary Angiography.

The differences in angiographic characteristics and cardiovascular (CV) risk factors between coronary artery aneurysm (CAA) and coronary artery ectasia (CAE) have not been compared systematically. Of 10 876 patients undergoing coronary angiography, patients with CAA (n = 85) and CAE (n = 51) were screened. The prevalence of CAA was greater than that of CAE ( P < .05). The right coronary artery was the most involved (70.6%) in CAE compared with left circumflex (52.9%) and left anterior descending (41.2%). Coronary artery aneurysm coexisted with coronary artery disease (CAD) more frequently than CAE ( P = .002), and the modified Gensini score of CAA was also higher than that of CAE ( P < .001). The average maximum diameter was smaller, and corrected Thrombolysis in Myocardial Infarction (TIMI) frame count was lower in CAA than CAE in all 3 coronary arteries ( P < .001). Multivariate analysis showed that hyperlipidemia ( P = .02), smoking ( P = .04), and family history of CAD ( P = .02) were the independent variables most strongly associated with CAA, but not CAE. This study suggests that there are significant differences in coronary angiographic characteristics and CV risk factors between CAA and CAE.

Effect of genetic and coexisting polymorphisms on platelet response to clopidogrel in Chinese Han patients with acute coronary syndrome.

Polymorphisms of CYP2C19 are associated with platelet response to clopidogrel. This study was conducted to evaluate the contribution of the previously identified polymorphisms to the response of clopidogrel in a cohort of Chinese Han patients. A total of 222 acute coronary syndrome patients undergoing percutaneous coronary intervention treated with clopidogrel were enrolled from September 2012 to June 2013. Residual platelet aggregations for all patients were measured by the Verify Now P2Y12 system. Sixteen single-nucleotide polymorphisms among nine genes were genotyped including CYP2C19, ABCB1 and PON1. In this study, CYP2C19*2 and CYP2C19*17 were strongly associated with higher platelet aggregation and lower platelet aggregation to clopidogrel treatment, respectively (P <0.001). Patients with CYP2C19*2 allele had a higher risk of high on-treatment platelet reactivity than non carriers (adjusted OR, 5.434; 95% CI, 1.918-15.399, P =0.01). The coexistence of CYP2B6*9 (rs8192719) and P2Y12 (rs2046934) and the coexistence of CYP2B6*1B (rs7254579) and P2Y12 (rs2046934) were also associated with poor response to clopidogrel. No significant relation of CYP2C19*3 and other polymorphisms to the platelet aggregation was found. In conclusion, CYP2C19*2, CYP2C19*17 coexistence of CYP2B6*9 (rs8192719) and P2Y12 (rs2046934) and coexistence of CYP2B6*1B (rs7254579) and P2Y12 (rs2046934) were identified to be associated with response to clopidogrel treatment in Chinese Han patients.

Phenotypic transformation of smooth muscle cells from porcine coronary arteries is associated with connexin 43.

The current study aimed to investigate the relevance of the gap junction protein connexin Cx43 in coronary artery smooth muscle cell (SMC) heterogeneity and coronary artery restenosis. SMCs were isolated from the coronary artery of 3­month­old pigs using enzymatic digestion. Two distinct SMC populations were isolated: Rhomboid (R) and spindle­shaped (S) cells. S­SMCs exhibited relatively lower rates of proliferation, exhibiting a classic ''hills­and valleys'' growth pattern; R­SMCs displayed increased proliferation rates, growing as mono­ or multi­layers. Immunofluorescent staining, polymerase chain reaction and western blotting were used to assess the expression of Cx40 and Cx43 in SMCs. For further evaluation, cultured SMCs were treated with 10 ng/ml platelet­derived growth factor (PDGF)­BB with or without the gap junction blocker 18α­glycyrrhetinic acid. Stent­induced restenosis was assessed in vivo. Different expression patterns were observed for Cx40 and Cx43 in R­ and S­SMCs. Cx40 was the most abundant Cx in S­SMCs, whereas CX43 was identified at relatively higher levels than Cx40 in R­SMCs. Notably, PDGF­BB converted S­SMCs to R­SMCs, with increased Cx43 expression, while 18α­glycyrrhetinic acid inhibited the PDGF­BB­induced phenotypic alterations in S­SMCs. Additionally, restenosis was confirmed in pigs 1­month subsequent to stent placement. R­SMCs were the major cell population isolated from stent­induced restenosis artery tissues, and exhibited markedly increased Cx43 expression, in accordance with the in vitro data described above. In conclusion, the phenotypic transformation of coronary artery SMCs is closely associated with Cx43, which is involved in restenosis. These observations provide a basis for the use of Cx43 as a novel target in restenosis prevention.

Combination of P2Y12 reaction unit and percentage of platelet inhibition assessed by VerifyNow P2Y12 assay is a useful predictor of long-term clinical outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

INTRODUCTION: High on-treatment platelet reactivity is a well-known risk factor for adverse events in patients undergoing percutaneous coronary intervention (PCI). This study was to investigate the value of a novel platelet reactivity-based system, named the COP-INH (COmbination of P2Y12 reaction unit [PRU] and percentage of platelet inhibition [%INH]), assessed by VerifyNow P2Y12 assay, for predicting the long-term ischaemic events in patients with acute coronary syndrome (ACS) undergoing PCI. MATERIALS AND METHODS: The COP-INH was calculated on the basis of data obtained at 30days after PCI: patients with both an elevated PRU (≥230) and decreased %INH (<40%) were allocated a score of 2, and patients showing one or neither were allocated a score of 1 or 0, respectively. The primary endpoint was the composite of cardiovascular death, nonfatal myocardial infarction, and target vessel revascularization at 1year follow-up. The relationship between the COP-INH score and primary endpoint was analyzed. RESULTS: 207 patients were enrolled. Baseline characteristics were similar between patients with COP-INH=2 and patients with COP-INH=1 or 0, except for diabetes mellitus (43.8% vs. 21.7%, p=0.015) and previous coronary artery bypass grafting (CABG) (21.9% vs. 6.86%, p=0.007). During the observation period, the incidence of major adverse cardiovascular events (MACE) in patients with COP-INH=2 was significantly higher than patients with COP-INH=1 or 0 (18.8% vs. 4.6%, p=0.007). Multivariate analysis of clinical characteristics and platelet reactivity selected by univariate analysis showed that the COP-INH=2 was an independent predictor of MACE in patients with ACS undergoing PCI (OR 2.745; 95% CI 1.369-9.851; p=0.024), whereas neither PRU≥230 nor %INH<40% was. CONCLUSION: The COP-INH is considered to be a useful predictor of long-term ischaemic events of patients with ACS undergoing PCI.

Remedial hydration reduces the incidence of contrast-induced nephropathy and short-term adverse events in patients with ST-segment elevation myocardial infarction: a single-center, randomized trial.

OBJECTIVE: The aim of this study was to investigate whether remedial hydration (RH) reduces the incidence of contrast-induced nephropathy (CIN) and short-term adverse events in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). METHODS: A total of 216 consecutive STEMI patients were prospectively and randomly assigned into two groups: 108 patients in the RH group and 108 patients in the no RH (control) group. The serum creatinine (SCr) and creatinine clearance (CCr) levels were measured on admission and at 24, 48 and 72 hours after primary PCI. The rates of CIN and short-term adverse events were analyzed for each group. After surgery, the patients were categorized into four groups according to the Mehran risk score: low (≤5, n =98), moderate (6-10, n=56), high (11-15, n=40) or very high (≥16, n=22). RESULTS: The incidence of CIN in the RH group was lower than that observed in the control group (22/108; 20.4% vs. 38/108; 35.2%, p<0.05). The subgroup analysis showed that the rate of CIN was lower in the moderate (6/29; 20.7% vs. 13/30; 43.3%, p<0.10) and significantly lower in both the high (5/21; 23.8% vs. 10/18; 55.6%, p<0.05) and very high score groups (3/12; 25.0% vs. 8/12; 66.7%, p<0.05) among the RH patients compared to the controls. At 24, 48 and 72 hours after PCI, the patients in the RH group exhibited lower SCr levels and higher CCr levels than the patients in the control group (both p<0.05). A lower incidence of in-hospital clinical events was also observed in the RH group. CONCLUSION: Remedial hydration decreases the occurrence of CIN and improves the short-term prognosis of STEMI patients undergoing primary PCI.