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Background Endothelial dysfunction, a hallmark of diabetes, is a critical and initiating contributor to the pathogenesis of diabetic cardiovascular complications. However, the underlying mechanisms are still not fully understood. Ferroptosis is a newly defined regulated cell death driven by cellular metabolism and iron-dependent lipid peroxidation. Although the involvement of ferroptosis in disease pathogenesis has been shown in cancers and degenerative diseases, the participation of ferroptosis in the pathogenesis of diabetic endothelial dysfunction remains unclear. Aim To examine the role of ferroptosis in diabetes-induced endothelial dysfunction and the underlying mechanisms. Methods Human umbilical vein endothelial cells (HUVECs) were treated with high glucose (HG), interleukin-1β (IL-1β), and ferroptosis inhibitor, and then the cell viability, reactive oxygen species (ROS), and ferroptosis-related marker protein were tested. To further determine whether the p53-xCT (the substrate-specific subunit of system Xc-)-glutathione (GSH) axis is involved in HG and IL-1β induced ferroptosis, HUVECs were transiently transfected with p53 small interfering ribonucleic acid or NC small interfering ribonucleic acid and then treated with HG and IL-1β. Cell viability, ROS, and ferroptosis-related marker protein were then assessed. In addition, we detected the xCT and p53 expression in the aorta of db/db mice. Results It was found that HG and IL-1β induced ferroptosis in HUVECs, as evidenced by the protective effect of the ferroptosis inhibitors, Deferoxamine and ferrostatin-1, resulting in increased lipid ROS and decreased cell viability. Mechanistically, activation of the p53-xCT-GSH axis induced by HG and IL-1β enhanced ferroptosis in HUVECs. In addition, a decrease in xCT and the presence of de-endothelialized areas were observed in the aortic endothelium of db/db mice. Conclusion Ferroptosis is involved in endothelial dysfunction and p53-xCT-GSH axis activation plays a crucial role in endothelial cell ferroptosis and endothelial dysfunction.

Background: Hypoxic pulmonary hypertension (HPH) is a devastating and incurable disease characterized by pulmonary vascular remodeling, resulting to right heart failure and even death. Accumulated evidence has confirmed long coding RNAs (lncRNAs) are involved in hypoxia induced pulmonary vascular remodeling in HPH. The exact mechanism of lncRNA in hypoxic pulmonary hypertension remains unclear. Methods：Microarray analysis was applied to investigate the profiles of lncRNA expression in pulmonary artery smooth muscle cells (PASMCs) cultured under hypoxia and normoxia condition. qRT-PCR was performed for the expression of lncRNAs, miRNA and mRNAs, western blot analysis was employed for detection the expression of proteins. CCK-8 and transwell chamber assay were applied for assessment of PASMC proliferation and migration, respectively. Besides, flow cytometry was performed for assessments of cell cycle progression. The binding between AC068039.4 and miR-26a-5p, miR-26a-5p and TRPC6 3’UTR were detected by dual luciferase reporter assay.Results：A total of 1211 lncRNAs (698 up-regulated and 513 down-regulated) were differently expressed in hypoxia induced PASMCs. Consistent with microarray analysis, quantitative PCR verified that AC068039.4 was obviously up-regulated in hypoxia induced PASMCs. Knocking down AC068039.4 alleviated proliferation and migration of PASMCs and regulated cell cycle progression through inhibiting cells entering the G0/G1 cell cycle phase. Further experiment indicated AC068039.4 promoted hypoxic PASMCs proliferation via sponging miR-26-5p. In addition, transient receptor potential canonical 6 (TRPC6) was confirmed to be a target gene of miR-26a-5p. Conclusion: In conclusion, downregulation of lncRNA AC068039.4 inhibited pulmonary vascular remodeling through AC068039.4/miR-26a-5p/TRPC6 axis, providing new therapeutic insights for the treatment of HPH.

This review paper focuses on the genetic contribution, in particular, the association of Apolipoprotein E gene polymorphism to lipid abnormality and subsequent acute coronary syndrome in Han Chinese of China. Many researches have been published pertaining the influence of ApoE gene polymorphism on coronary artery disease, dyslipidemia and the response of statin in Han Chinese. Most of the studies in Han Chinese like other populations demonstrated that ApoE 4 allele genetically predisposes coronary artery disease, acute coronary syndrome, severity of occlusion of coronary artery and higher incidence of major adverse cardiovascular events (In Han Chinese, ApoE allele carriers demonstrated 85% increase in major adverse cardiovascular events (MACE) in six months follow up). In addition, ApoE4 allele carrier also showed both increased in LDL level and decrease response to statin therapy in dyslipidemic Han Chinese. On the other hand, ApoE2 carrier is scavenger of cholesterol and triglyceride from the blood; thus it is cardiovascular-protective. Despite positive relationship between ApoE gene polymorphism and cardiovascular pathologies, prognostic outcome and resistance to intervention, this area of research still requires extensive investigation in Han Chinese. Because, several other studies revealed either negative effect or showed no effect by ApoE gene polymorphism on cardiovascular disease. Some of the causes of such debatable results could be explained by factors such as diminutive frequency allele and expression of ApoE gene in coronary heart disease. This part of the research yet requires extensive study with bulkier sample size and retrospective in nature, in order to ascertain the influence of ApoE genotype on lipid, anti-hyperlipidemic agent and coronary heart disease. Such studies could assist us to confirm whether to test healthier subjects to predict genetic risk of coronary heart disease in Han Chinese population. The aim of this review paper is to critically analyze the effect of ApoE gene on the occurrence of coronary heart disease in Han Chinese.

Pulmonary hypertension (PH) is a life-threatening cardiopulmonary condition caused by several pathogenic factors. All types of PH are characterized by the excessive proliferation of pulmonary artery endothelial cells and pulmonary artery smooth muscle cells, apoptosis resistance, pulmonary vascular remodeling, sustained elevated pulmonary arterial pressure, right heart failure and even death. Over the past decade, next generation sequencing, particularly RNA-sequencing, has identified some long non-coding RNAs (lncRNAs) that may act as regulators of cell differentiation, proliferation and apoptosis. Studies have shown that lncRNAs are closely associated with the development of several diseases, including cardiovascular diseases. In addition, a number of studies have reported that lncRNAs, including maternally expressed gene 3, metastasis-associated lung adenocarcinoma transcript 1, taurine upregulated 1 and cancer susceptibility candidate 2, serve important roles in the pathogenesis of PH. Despite the development of novel drug treatments, the mortality rate of PH remains high with no evident downward trend. Therefore, certain lncRNAs may be considered as therapeutic targets for the treatment of incurable PH. The present review summarizes the latest research on lncRNAs and PH, aiming to briefly describe PH-associated lncRNAs and their mechanisms of action.

Contrast-induced acute kidney injury (CI-AKI) is a serious complication of percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI). Early identification of high-risk patients has an essential role in preventing CI-AKI. This study was designed to evaluate the predictive value of d-dimer, a marker of thrombosis and hypercoagulable state, for CI-AKI and prognosis in patients with STEMI. We included 400 patients with STEMI who underwent PCI. The patients were subdivided into 4 groups according to d-dimer level using the 4-quantile method. Contrast-induced acute kidney injury occurred in 66 (16.5%) patients. The incidence of CI-AKI in the highest quartile of the d-dimer groups (29.0%) was higher than that in the other 3 groups. Multivariable logistic regression showed that a low d-dimer level was significantly associated with a decreased risk of CI-AKI independent of confounding factors, with an odds ratio (OR) of 0.487 (95% CI: 0.178-0.931, P = 0.041) for those in the first quartile compared with those in the highest quartile. Age (OR: 1.047, 95% CI: 1.003-1.092), diabetes mellitus (OR: 5.896, 95% CI: 2.496-13.927), anemia (OR: 3.488, 95% CI: 1.308-9.306), and total bilirubin (OR: 0.946, 95% CI: 0.904-0.992) were independent predictors of CI-AKI. The incidence of major adverse cardiovascular and cerebral events and all-cause mortality within 30 days, 6 months, and 1 year after PCI in the highest quartile of the d-dimer groups were higher than those in the other 3 groups. In conclusion, increasing d-dimer levels were independently associated with the incidence of CI-AKI and adverse outcomes in patients with STEMI after PCI.

Sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) pumps take up Ca2+ from the cytoplasm to maintain the balance of intracellular Ca2+. A decline in expression or activity of SERCA results in persistent store-operated calcium entry (SOCE). In cardiomyocytes as well as vascular smooth muscle cells (SMCs), SERCA2 acts as an important regulator of calcium cycling. The purpose of this study is to identify and better understand the role of transglutaminases2 (TG2) as a key factor involved in SERCA2 serotonination (s-SERCA2) and to elucidate the underlying mechanism of action. Human pulmonary venous smooth muscle cell in normal pulmonary lobe were isolated and cultured in vitro. Establishment of hypoxic pulmonary hypertension model in wild type and TG2 knockout mice. SERCA2 serotonylation was analyzed by co-(immunoprecipitation) IP when the TG2 gene silenced or overexpressed under normoxia and hypoxia in vivo and in vitro. Intracellular calcium ion was measured by using Fluo-4AM probe under normoxia and hypoxia. Real-time (RT)-PCR and Western blot analyzed expression of TG2, TRPC1, and TRPC6 under normoxia and hypoxia. Bioactivity of cells were analyzed by using Cell Counting Kit (CCK)-8, flow cytometry, wound healing, RT-PCR, and Western blot under PST-2744 and cyclopiazonic acid. We confirmed that 1) hypoxia enhanced the expression and activity of TG2, and 2) hypoxia increased the basal intracellular Ca2+ concentration ([Ca2+]i) and SOCE through activating TRPC6 on human pulmonary vein smooth muscle cells (hPVSMC). Then, we investigated the effects of overexpression and downregulation of the TG2 gene on the activity of SERCA2, s-SERCA2, basal [Ca2+]i, and SOCE under normoxia and hypoxia in vitro, and investigated the activity of SERCA2 and s-SERCA2 in vivo, respectively. We confirmed that SERCA2 serotonylation inhibited the activity of SERCA2 and increased the Ca2+ influx, and that hypoxia induced TG2-mediated SERCA2 serotonylation both in vivo and in vitro. Furthermore, we investigated the effect of TG2 activity on the biological behavior of hPVSMC by using an inhibitor and agonist of SERCA2, respectively. Finally, we confirmed that chronic hypoxia cannot increase vessel wall thickness, the right ventricular systolic pressure (RVSP), and right ventricular hypertrophy index (RVHI) of vascular smooth muscle-specific Tgm2−/− mice. These results indicated that hypoxia promoted TG2-mediated SERCA2 serotonylation, thereby leading to inhibition of SERCA2 activity, which further increased the calcium influx through the TRPC6 channel. Furthermore, tissue-specific conditional TG2 knockout mice prevents the development of pulmonary hypertension caused by hypoxia. In summary, we uncovered a new target (TG2) for treatment of chronic hypoxic pulmonary hypertension (CHPH).

Platelet-derived growth factor-BB (PDGF-BB) can induce the proliferation, migration, and phenotypic modulation of vascular smooth muscle cells (VSMCs). We used patch clamp methods to study the effects of PDGF-BB on inward rectifier K+ channel 2.1 (Kir2.1) channels in rat thoracic aorta VSMCs (RASMCs). PDGF-BB (25 ng/mL) increased Kir2.x currents (−11.81±2.47 pA/pF, P<0.05 vs. CON, n=10). Ba2+(50 μM) decreased Kir2.x currents (−2.13±0.23 pA/pF, P<0.05 vs. CON, n=10), which were promoted by PDGF-BB (−6.98±1.03 pA/pF). PDGF-BB specifically activates Kir2.1 but not Kir2.2 and Kir2.3 channels in HEK-293 cells. The PDGF-BB-induced stimulation of Kir2.1 currents was blocked by the PDGF-BB receptor β (PDGF-BBRβ) inhibitor AG1295 and was not affected by the PDGF-BBRα inhibitor AG1296. The PDGF-BB-induced stimulation of Kir2.1 currents was blocked by the protein kinase A inhibitor Rp-8-CPT-cAMPs; however, the antagonist of protein kinase B (GSK690693) had marginal effects on current activity. The PDGF-BB-induced stimulation of Kir2.1 currents was enhanced by forskolin, an adenylyl cyclase (AC) activator, and was blocked by the AC inhibitor SQ22536. We conclude that PDGF-BB increases Kir2.1 currents via PDGF-BBRβ through activation of cAMP-PKA signaling in RASMCs.

Background and ObjectivesTriglyceride-glucose (TyG) is an emerging vital indicator of insulin resistance and is associated with increased risk of T2DM and cardiovascular events. We aimed to explore the TyG index and contrast-induced acute kidney injury (CI-AKI) in patients with type 2 diabetes who underwent coronary angiology.MethodsThis study enrolled 928 patients with suspected coronary artery disease who underwent coronary angiology or percutaneous coronary intervention in Zhongda hospital. Patient data were divided into quartiles according to the TyG index: group 1: TyG ≤ 8.62; group 2: 8.629.45. CI-AKI was diagnosed according to the KIDIGO criteria. Demographic data, hematological parameters, coronary angiology data, and medications were all recorded. We calculated the TyG index using the following formula: ln [fasting TG (mg/dL)×FPG (mg/dL)/2].ResultsPatients who developed CI-AKI exhibited significantly higher TyG index levels compared to patients who did not develop CI-AKI. The incidence of CI-AKI sharply increased with increasing TyG. Univariate and multivariate analysis identified TyG as an independent risk factor for CI-AKI. The AUC of the ROC curve was as high as 0.728 when the value of TyG was 8.88. The corresponding sensitivity was as high as 94.9%. Adding the variable TyG to the model for predicting CI-AKI risk further increased the predictive value of the model from 80.4% to 82%.ConclusionsHigh TyG is closely associated with increased incidence of CI-AKI, demonstrating that TyG is an independent risk factor for CI-AKI. TyG has potentially predictive value for CI-AKI and may play a crucial role in risk stratification in clinical practice.

Hypoxia-induced pulmonary hypertension is a life-threatening disease arising from a progressive increase in pulmonary vascular resistance, irreversible pulmonary vascular remodeling and resulting in right ventricular failure. Recent studies suggested that pulmonary artery smooth muscle cell proliferation and migration played an important role in the pathogenesis of hypoxia-induced pulmonary hypertension. However, the mechanisms of hypoxia-induced pulmonary hypertension are complicated and largely unclear. In this study, we discovered that lncRNA MEG3 was down-regulated in human pulmonary artery smooth muscle cell in hypoxia, and inhibition of MEG3 promoted the cell proliferation and cell migration in both normal and hypoxia condition. Further study demonstrated that MEG3 exerted its function via regulation of miR-21 expression in both normal and hypoxia condition. In addition, we displayed the modulation of PTEN by miR-21 and their role in hypoxia. Ultimately, our study illustrated that MEG3 exerts its role via miR-21/PTEN axis in human pulmonary artery smooth muscle cell under both normal and hypoxia conditions.

Background We aim to find out the relationship between random blood glucose (RBG), fasting blood glucose (FBG) and in-hospital adverse events in ST-segment elevation acute myocardial infarction (STEMI) patients. We evaluate and compare the predictive value of RBG and FBG on in-hospital adverse events, and give an appropriate cut-off value of RBG and FBG. Method A retrospective study enrolled 958 consecutive AMI patients undergoing emergency coronary angiography at Zhongda Hospital were enrolled from January 1, 2016, to December 31, 2018 was performed. RBG and FBG, baseline data and adverse events were recorded. Major adverse cardiovascular and cerebrovascular events (MACCE) were defined as death, nonfatal recurrent myocardial infarction and stroke. Other adverse events included malignant arrhythmia, cardiac shock and hemorrhage. Patients with RBG > 11.1 mmol/L were divided into elevated RBG group. Patients with FBG > 6.1 mmol/L were divided into elevated FBG group. The incidence of in-hospital adverse events were compared in elevated RBG/FBG group and the control group. ROC curve was used to evaluate the predictive value of RBG and FBG on in-hospital adverse events. Result The incidence of death, hemorrhage, cardiac shock and malignant arrhythmia significantly increases in elevated RBG and FBG group. Binary logistic regression showed that age, hypertension, diabetes, FBG and RBG were independent risk factors for in-hospital adverse events in STEMI patients. The AUC and 95% CI of RBG and FBG in predicting death of AMI patients were 0.789, 0.759~0.816; 0.810, 0.783~0.835, respectively. The cut-off values ​were 13.82 and 7.35 mmol/L. RBG and FBG also had fine predictive value on cardiac shock and malignant arrhythmia, no statistical difference was found in the predictive value on in-hospital adverse events (P = 0.462, P = 0.570, P = 0.694). Conclusion Incidence of in-hospital adverse events significantly increases in AMI patients combined with elevated RBG or FBG. Both RBG and FBG were independent risk factors for in-hospital adverse events, they had good value on predicting in-hospital adverse events and there was no statistical difference in their predictive value.

Anaemia and high haemoglobin levels are common in ST elevation myocardial infarction (STEMI) patients, but the effect of the haemoglobin level on the prognosis of STEMI patients remains in dispute. This study aimed to evaluate the prognostic value of the haemoglobin level combined with the CAMI-STEMI score in STEMI patients after percutaneous coronary intervention (PCI). We included 360 STEMI patients who underwent PCI. The patients were divided into 3 groups according to the first haemoglobin value after PCI. Clinical characteristics and the incidence of major adverse cardiovascular and cerebral events (MACCE) during the follow-up period were recorded. The incidence of MACCE in the 3 groups increased with a decrease in the haemoglobin level. Multivariate regression analysis showed that the CAMI-STEMI score was an independent predictor of MACCE incidence at 30 days after PCI and that anaemia was an independent predictor of MACCE incidence at 6 months and 1 year after PCI. A high haemoglobin level was an independent predictor of MACCE incidence at 1 year after PCI. The area under receiver operating characteristic curves (AUCs) of the haemoglobin level, CAMI-STEMI score, and haemoglobin level combined with CAMI-STEMI score predicting the occurrence of MACCE in STEMI patients within 30 days after PCI were 0.604, 0.614, and 0.639, respectively. In conclusion, The CAMI-STEMI score was an independent predictor of MACCE incidence at 30 days after PCI. The haemoglobin level combined with the CAMI-STEMI score improved the predictive value of MACCE in STEMI patients within 30 days after PCI.Trial Registration. This trial was a prospective cohort study and registered withChiCTR-ROC-17011542.

Background and Aims. CIN is a major and serious complication following PCI in patients with ACS. It is unclear whether a higher serum ferritin level is associated with an increased risk of CIN in high-risk patients. Thus, we conducted this study to assess the predictive value of SF for the risk of CIN after PCI.Methods. We prospectively examined SF levels in 548 patients with ACS before undergoing PCI. Multivariate logistic regression analysis was used to analyze the independent risk factors for CIN. The ROC analysis was performed to evaluate the predictive value of SF for CIN.Results. CIN occurred in 96 patients. Baseline SF was higher in patients who developed CIN compared to those who did not (257.05±93.98versus211.67±106.65;P<0.001). Multivariate logistic regression analysis showed that SF was an independent predictor of CIN (OR, 1.008; 95% CI, 1.003–1.013;P=0.002). The area under ROC curve for SF was 0.629, and SF > 180.9 μg/L predicted CIN with sensitivity of 80.2% and specificity of 41.4%.Conclusion. Our data show that a higher SF level was significantly associated with an increased risk of CIN after PCI.

Endothelial cells (ECs) primarily rely on glycolysis for their energy metabolism, and the final product of glycolysis—lactate—is transferred out of cells via monocarboxylate transporter 4 (MCT4). We previously showed that MCT4 downregulation is involved in diabetic endothelial injury. However, the underlying regulatory mechanisms of MCT4 in diabetes remain unclear. This study showed that miR-425-5p was significantly upregulated in diabetic patients and human umbilical vein endothelial cells (HUVECs) treated with high glucose (HG) and interleukin-1β (IL-1β). MCT4 was shown to be a direct target gene of miR‐425‐5p, and miR-425-5p expression led to MCT4 downregulation, lactate accumulation and increased apoptosis in HUVECs. Furthermore, the results indicated that NF-κB signaling activation increased miR-425-5p levels and induced MCT4 downregulation, lactate accumulation and apoptosis in HUVECs. In conclusion, NF-κB/miR-425-5p/MCT4 axis activation plays a crucial role in the EC injury induced by HG and IL-1β.

Background and Aims. Contrast-induced nephropathy (CIN) is a relatively infrequent complication after percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI). However, little is known about the association between cytochrome c (cyt c) and increased risk of CIN. We conducted this study to explore the impact of serum cyt c on the occurrence of CIN. Methods. We prospectively examined cyt c levels before undergoing PCI in 240 patients with STEMI. The logistic regression was performed to identify the independent risk factors for the occurrence of CIN. The receiver operating characteristic (ROC) analysis was employed to evaluate the predictive value of cyt c for the occurrence of CIN. Results. 29 patients (12.1%) had developed CIN after the PCI procedure. The cyt c levels at baseline were significantly higher in patients who developed CIN than those in non-CIN group (0.65±0.08 versus 0.58±0.1; P = 0.001). The multivariate logistic regression showed that cyt c was an independent risk factor for the occurrence of CIN (OR, 7.421; 95% CI, 6.471–20.741; P = 0.034) after adjusting for age, history of hypertension and diabetes mellitus, levels of creatinine, uric acid, and glucose. The ROC curve analysis showed that the area under the curve of cyt c was 0.697 (95% CI, 0.611–0.783; P = 0.001), and cyt c > 0.605 ng/mL predicted CIN with sensitivity of 79.3% and specificity of 56.9%. Conclusion. Our results show that a higher cyt c level was significantly associated with the occurrence of CIN after PCI in STEMI patients. This study has been registered in the Chinese Clinical Trial Registry. The clinical trial registration number is ChiCTR1800019368.

Background. Renal vasoconstriction, oxidative stress, endothelial dysfunction, and apoptosis are the major causes of contrast-induced nephropathy (CIN). The aim of this study was to evaluate the protective effects of enalapril maleate and folic acid tablets on CIN in diabetic rats.Methods. Thirty-two Sprague-Dawley rats were divided into four groups: CIN (C), CIN + enalapril maleate (CE), CIN + folic acid (CF), and CIN + enalapril maleate and folic acid tablets (CEF). CE, CF, and CEF rats were treated orally with enalapril maleate, folic acid, or enalapril maleate and folic acid tablets, respectively, for 5 days. CIN was induced in all groups followed by analyzed biochemical parameters, oxidative stress markers, endothelial dysfunction parameters, renal histopathology, and TUNEL staining.Results. Serum creatinine, blood urea nitrogen, and malondialdehyde levels were lower in the CEF group than in the C group. Homocysteine, superoxide dismutase, glutathione peroxidase, and nitric oxide levels were higher in the CEF group than in the C group. Histopathology scores and percentage of apoptotic kidney cells in the CEF group were significantly decreased compared with those in the C group.Conclusions. These results suggest that enalapril maleate and folic acid tablets have a protective effect against CIN in diabetic rats.

Background:Currently, the role of angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor antagonist (ARB) in CIN is paradoxical due to important differences in study design and study participant characteristics. We speculated that enalapril and folic acid tablets may have better protection on kidney target. Aim: To explore the impact of enalapril and folic acid tablet on contrast-induced nephropathy (CIN) in patients with mild renal insufficiency after percutaneous coronary intervention (PCI). Method: A total of 816 patients undergoing selective PCI, between January 2013 and December 2016, were enrolled in a prospective cohort. Patients were divided into enalapril and folic acid tablets treatment group (n=233) (Namely, intervention group) and non ACEI/ARB treatment group (n=583) (Namely, control group). Baseline data were compared among 2 groups, and multivariate logistic regression analysis was used to analyze the independent risk factors for CIN. The clinical events within 1-month after contrast were recorded. Result: The incidence of CIN was lower in the intervention group than in the control group (8.2% (19/233) vs. 13.4% (78/583), P=0.041). Multivariate analysis found that age odds ratio [ (OR)=1.078, P=0.001] and hypertension (OR=3.376, P=0.004), hyperhomocysteinemia (OR=3.339, P=0.001) were independent risk factors of CIN. However, eGFR was the dependent protector factor of CIN (OR=0.957, P=0.013). During 1 month follow-up, the rate of recurrent angina pectoris was lower in the intervention group than in the control group (P�?0.05), however, there were no significant differences between the 2 groups in the rates of worsening renal failure or hospitalization for worsening renal failure, dialysis/hemofiltration, acute heart failure, myocardial infarction recurrence and all-cause death (all, P�?0.05). Conclusion: The treatment with enalapril and folic acid tablet may prevent the occurrence of CIN in patients with mild renal insufficiency after PCI.

// Boqian Zhu 1, * , Xinmin Si 2, * , Yaoyao Gong 2, * , Gaoliang Yan 1 , Dong Wang 1 , Yong Qiao 1 , Bo Liu 1 , Jiantong Hou 1 and Chengchun Tang 1, * 1 Department of Cardiology, Zhongda Hospital, Southeast University, Nanjing, China 2 Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China * These authors contributed equally to this work Correspondence to: Chengchun Tang, email: tangchengchun@medmail.com.cn Keywords: premature coronary artery disease, G894T, Glu298Asp, polymorphism, endothelial nitric oxide synthase Received: March 02, 2017 Accepted: July 29, 2017 Published: August 23, 2017 ABSTRACT Previous epidemiological studies have suggested that genetic factors are more likely to influence the development of premature coronary artery disease (CAD) than disease in older patients. Several studies have evaluated the association between the G894T polymorphism located in an exon of endothelial nitric oxide synthase (eNOS) and the risk of premature CAD. However, the findings were inconsistent. Thus, we performed a meta-analysis to clarify the association; we conducted both overall and subgroup analyses. Odds ratios and 95% confidence interval were calculated to evaluate the association between the G894T polymorphism and the risk of premature CAD. Overall analysis revealed a significant association. Subgroup analysis in terms of ethnicity revealed a significant association, in all models evaluated, between the G894T polymorphism and susceptibility to premature CAD in mixed population. In contrast, no such association was evident in Caucasians and Asians. On further subgroup analysis based on the premature CAD subtypes, we found that the G894T polymorphism was correlated with premature myocardial infarction (MI) but not with premature CAD without MI. In conclusion, we confirmed that the eNOS G894T polymorphism is a risk factor for premature CAD, particularly in those suffering premature MI.

Intimal hyperplasia, the key event of arterial restenosis, is a result of cell proliferation and cell migration. Atorvastatin exerts an inhibitory effect on cell proliferation and migration, but the mechanism remains largely unknown. p16, as a well-known tumor suppressor, was also reported to suppress cell growth and migration, but with an unclear mechanism. In this study, we demonstrated that atorvastatin represses cell proliferation and migration in vascular smooth muscle cells (VSMCs) and that this process is mediated by p16. Furthermore, we found that DNA methylation in the p16 promoter was reduced and p16 expression was restored in VSMCs treated with 5-aza-2'-deoxycytidine or atorvastatin. However, the effect was absent when DNA methyltransferase 1 (DNMT1) was knocked down with RNA interference. These observations demonstrated that atorvastatin regulates p16 expression via DNMT1-induced DNA methylation in the p16 promoter. In addition, we found that the mitogen-activated protein kinase (MAPK) pathway was involved in the regulation of p16 by DNMT1, and MAPK inhibitors partially released the effects of atorvastatin on p16 and DNMT1. Finally, we illustrated that atorvastatin inhibits neointima formation and modulates p16 expression in balloon catheter-injured rat carotid artery. Taken together, we demonstrated that atorvastatin inhibits neointima formation through inducing p16 expression by affecting DNA methylation in the p16 promoter region.

To explore the relationship between hyperhomocysteinemia (H-Hcy) and long-term outcome of coronary artery disease (CAD) patients after drug-eluting stent (DES) implantation in a single centre.A total of 1 408 consecutive patients implanted with DES in our department between March 2011 and January 2013 were enrolled in this prospective study. Patients were stratified into H-Hcy (Hcy≥10 µmol/L, n=798, 56.7%) and non-H-Hcy group (Hcy10 µmol/L, n=610, 43.3%). The clinical characteristics, coronary artery lesions, SYNTAX score and 1-year major adverse cardiac and cerebrovascular events (MACCE) were compared between the two groups.Compared with non-H-Hcy group, coronary artery stenosis was severer as shown by higher diseased arteries (2.11±0.87 vs. 1.91±0.82, P0.001), higher incidence of three diseased arteries (39.7% vs. 29.5%, P0.001) and higher SYNTAX score (36.99±29.66 vs. 27.39±22.70, P=0.001) in H-Hcy group. The 1-year incidence of MACCE was also higher in H-Hcy group compared with non-H-Hcy group(18.4% vs. 8.9%, P0.001). Multivariate Cox analysis showed that diabetes mellitus (OR=1.530, 95%CI 1.142-2.050, P=0.004), age (OR=1.065, 95%CI 1.038-1.093; P0.001), and Hcy (OR=1.019, 95%CI 1.005-1.033, P=0.009) are the independent predictors for 1-year MACCE.High Hcy level is correlated with the severity of coronary artery stenosis, and serves as an independent predictor of MACCE after stenting in CAD patients.

To explore the impact of plasma homocysteinemia(Hcy) on contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) patients.Consecutive 684 ACS patients undergoing first PCI in our department between January 2013 and December 2014 were prospectively enrolled.Patients were divided into 2 groups according to the pre-procedural plasma Hcy level: high-Hcy group (Hcy≥10 μmol/L, n=404) and control group (Hcy10 μmol/L, n=280). The CIN was defined as serum creatinine ≥ 44.2 μmol/L or 25% increase compared to baseline within 48-72 h after PCI.The baseline clinical data and the ratio of CIN were compared between the 2 groups.Multivariate logistic regression analysis was used to define the independent risk factors for CIN.CIN occurred in 133(19.4%) out of 684 enrolled patients, and the incidence of CIN was significantly higher in high Hcy group than in the control group (22.0%(89/404)vs. 15.7%(44/280), P=0.040). After adjusting the confounding factors, including age, acute myocardial infarction, co-morbidities(hypertension, diabetes mellitus, and old myocardial infarction), laboratory examination (level of cystatin C and uric acid), glomerular filtration rate, left ventricular ejection fraction, angiographic and procedural characteristics (3 diseased vessels, multiple stent implantation), treatment at admission (spironolactone, digoxin), multivariate logistic regression analysis showed that high Hcy was independently associated with the development of CIN (OR=1.70, 95%CI 1.60-2.64, P=0.021).Elevated Hcy prior PCI is an independent risk factor of CIN in ACS patients undergoing first PCI.