刘强
中国医学科学院阜外医院深圳医院 心血管内科
This study aims to determine the effect of exogenous hydrogen sulfide (H2S) under high glucose (HG)-induced injury in endothelial progenitor cells (EPCs), and to explore the possible underlying mechanisms. Mononuclear cells were isolated from the peripheral blood of healthy volunteers by density-gradient centrifugation and identified as late EPCs by immunofluorescence and flow cytometry. EPCs were treated with high concentrations of glucose, H2S, Baf-A1, 3-MA or rapamycin. Cell proliferation, cell migration and tube formation were measured using cell counting kit-8, Transwell migration and tube formation assays, respectively. Cellular autophagy flux was detected by RFP-GFP-LC3, and Western blotting was used to examine the protein expression levels of LC3B, P62, and phosphorylated endothelial nitric oxide synthase (eNOS) at Thr495 (p-eNOSThr495). Reactive oxygen species (ROS) levels were measured using a DHE probe. H2S and rapamycin significantly reversed the inhibitory effects of HG on the proliferation, migration, and tube formation of EPCs. Moreover, H2S and rapamycin led to an increase in the number of autophagosomes accompanied by a failure in lysosomal turnover of LC3-II or p62 and p-eNOSThr495 expression and ROS production under the HG condition. However, Baf-A1 and 3-MA reversed the effects of H2S on cell behavior. Collectively, exogenous H2S ameliorated HG-induced EPC dysfunction by promoting autophagic flux and decreasing ROS production by phosphorylating eNOSThr495.
Bioengineered 2022
Background:The present study aims to explore risk factors related to in-stent restenosis (ISR) in elderly patients with coronary heart disease and type 2 diabetes within 2 years after the first drug-eluting stent (DES) implantation.Methods:This case-control study retrospectively analyzed the clinical data of patients with coronary heart disease and diabetes undergoing percutaneous coronary intervention (PCI) in Shenzhen Sun Yat-sen Cardiovascular Hospital between January 2010 and March 2020. Univariate and multivariate models were used to assess independent factors for DES-ISR. Categorical principal component analysis of clinical variables was performed to determine important components for DES-ISR. Nomogram was constructed to quantitatively predict the probability of DES-ISR development. The diagnostic potential of clinical variables was determined by receiver operating characteristic curve.Results:In the derivation cohort, 1,741 cases were included in this study, and a total of 227 pairs of cases and controls were generated by propensity score matching. In the validation cohort, 102 cases were included with 19 cases (18.6%) with DES-ISR. Glomerular filtration rate <60 ml/min/1.73 m2, fasting blood glucose ≥6.5 mmol/L, multivessel coronary artery disease, coronary artery diffuse disease, PCI operation time (≥60 min), emergency PCI were associated with ISR. High Nomogram score was associated with the increased risk of ISR. Further analysis of the validation cohort showed that higher levels of HbA1c-coefficient of variation (CV) were significantly associated with the increased risk of ISR. HbA1c-CV exhibited good predictive ability for ISR in the validation cohort.Conclusions:In conclusion, the fasting blood glucose level during the perioperative period of emergency PCI and the long-term variation of HbA1c during the follow-up period are related to the incidence of DES-ISR and the degree of stenosis. Reducing blood glucose fluctuations may decrease the risk of DES-ISR.
Frontiers in cardiovascular medicine 2022
Introduction:Myocardial ischemia/reperfusion (I/R) injury is a leading cause of cardiac dysfunction. Circular RNAs (circRNAs) are involved in the pathogenesis of myocardial I/R injury. However, the functions and underlying mechanisms are unclear. The present study determined the role of circ-RHOJ.1 in regulating myocardial cell proliferation and apoptosis after I/R injury.Material and methods:Myocardial cells isolated from Sprague-Dawley rats were identified with an immunofluorescence assay using cardiac troponin T antibody. Expression of circ-RHOJ.1, miR-124-3p and neuregulin-1 (NRG1) mRNA was assessed with real-time quantitative polymerase chain reaction. NRG1 protein expression was evaluated with western blot and immunofluorescence assays. Dual-luciferase reporter assay was performed to confirm interaction between miR-124-3p and circ-RHOJ.1, and miR-124-3p and NRG1. Effects of circ-RHOJ.1 overexpression or miR-124-3p inhibition on cell proliferation and apoptosis were evaluated using cell counting kit (CCK)-8 assay and flow cytometry. Cytokines levels were analyzed with an enzyme-linked immunosorbent assay.Results:Myocardial cells were successfully isolated and had down-regulated expression of circ-RHOJ.1 and NRG1, and up-regulated expression of miR-124-3p after I/R injury. circ-RHOJ.1 acted as a sponge for miR-124-3p, and NRG1 served as a target gene of miR-124-3p. circ-RHOJ.1 overexpression or miR-124-3p inhibition increased interleukin (IL)-10 levels and reduced IL-2, IL-6, and tumor necrosis factor-α levels in myocardial cells after I/R injury. Functional assay results illustrated that circ-RHOJ.1 overexpression or miR-124-3p inhibition enhanced proliferation and inhibited apoptosis of myocardial cells after I/R injury.Conclusions:Circ-RHOJ.1 served as a molecular marker of myocardial I/R injury via regulation of miR-124-3p and NRG1 expression.
Archives of medical science : AMS 2022
OBJECTIVE:To investigate the effect of early use of ivabradine on left ventricular remodeling after primary percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI).METHODS:A total of 66 STEMI patients with sinus rhythm and the resting heart rate ≥80 bpm after successful emergency PCI were included. The patients in the test group were treated with ivabradine combined with metoprolol at 12 hr after PCI, while the control group was given only metoprolol orally. Their resting heart rate was controlled to <70 bpm at discharge and followed for 180 days. Heart rate and blood pressure were measured regularly. Echocardiogram was performed. N-terminal pro-B-type natriuretic peptide (NT-proBNP), high sensitivity troponin T, high sensitivity troponin I, and high sensitivity C-reactive protein were measured. The major adverse cardiovascular events during hospitalization and follow-up period were recorded.RESULTS:Compared with the control group, the heart rate of the test group decreased significantly (p < .05). Compared with the control group, the left ventricular end-diastolic volume and left ventricular end-systolic volume were significantly decreased while left ventricular ejection fraction was significantly increased in the test group at 90 days after operation. NT-proBNP of the test group was significantly lower than that of the control group at 7 days after operation (p < .05).CONCLUSION:For STEMI patients, early use of ivabradine combined with standard therapy such as β-blocker after successful reperfusion can achieve effective heart rate control, with great safety and tolerance. But the effect of ivabradine on left ventricular remodeling is uncertain.
Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc 2021
AIMS:The relationship between baseline base excess (BE) and survival outcomes in patients with congestive heart failure (CHF) is unclear. Therefore, we aimed to investigate this relationship based on the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) database (v1.4).METHODS AND RESULTS:This retrospective cohort study included 5956 adult patients with CHF from the MIMIC-III database from 2001 to 2012. Using the Cox proportional-hazard analysis and Kaplan-Meier plot, we evaluated the relationship between baseline BE and all-cause death at 1 year after admission to the intensive care unit. At the 1 year follow-up, 2104 participants (35.3%) had died. There was an association between BE and all-cause death (log-rank test P < 0.0001). In the Cox regression model adjusted for demographic and clinical variables, the risk of all-cause death in the first (BE ≤ -8), second (-8 < BE ≤ -3), fourth (2 < BE ≤ 7), and fifth (BE > 7) BE groups was significantly higher than that in the third BE group (-3 < BE ≤ 2) [hazard ratio (HR) 1.99, 95% confidence interval (CI) 1.62-2.43, HR 1.40, 95% CI 1.23-1.60, HR 1.46, 95% CI 1.26-1.69, and HR 1.68, 95% 1.33-2.12, respectively]. Similar results were observed when BE was modelled as a continuous variable using a Cox regression model with a restricted cubic spline.CONCLUSIONS:This study demonstrated the existence of a U-shaped relationship between BE and survival outcome in patients with CHF. Both low and high BE increased the risk of all-cause mortality.
ESC heart failure 2021
BACKGROUND:Double kissing (DK) crush approach for patients with coronary bifurcation lesions, particularly localized at distal left main or lesions with increased complexity, is associated with significant reduction in clinical events when compared with provisional stenting. Recently, randomized clinical trial has demonstrated the net clinical benefits by intravascular ultrasound (IVUS)-guided implantation of drug-eluting stent in all-comers. However, the improvement in clinical outcome after DK crush treatment guided by IVUS over angiography guidance for patients with complex bifurcation lesions have never been studied in a randomized fashion.TRIAL DESIGN:DKCRUSH VIII study is a prospective, multicenter, randomized controlled trial designed to assess superiority of IVUS-guided vs angiography-guided DK crush stenting in patients with complex bifurcation lesions according to DEFINITION criteria. A total of 556 patients with complex bifurcation lesions will be randomly (1:1 of ratio) assigned to IVUS-guided or angiography-guided DK crush stenting group. The primary end point is the rate of 12-month target vessel failure, including cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. The secondary end points consist of the individual component of primary end point, all-cause death, myocardial infarction, and in-stent restenosis. The safety end point is the incidence of definite or probable stent thrombosis. An angiographic follow-up will be performed for all patients at 13 months and clinical follow-up will be continued annually until 3 years after the index procedure.CONCLUSIONS:DKCRUSH VIII trial is the first study designed to evaluate the differences in efficacy and safety between IVUS-guided and angiography-guided DK crush stenting in patients with complex true bifurcation lesions. This study will also provide IVUS-derived criteria to define optimal DK crush stenting for bifurcation lesions at higher complexity.
American heart journal 2021
This study evaluated the benefit of dual therapy in reducing ischemic events in atrial fibrillation (AF) patients presenting with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). We searched PubMed, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) comparing dual and triple therapies (oral anticoagulation plus aspirin and P2Y12 inhibitor) for AF patients with ACS or those undergoing PCI. The composite primary outcome included all-cause death, myocardial infarction (MI), stent thrombosis (ST), or stroke. Relative risk (RR) and the corresponding 95% confidence interval (CI) was used as the measure of effect size. Four RCTs with 10,969 patients were included. Dual therapy had a higher event rate of primary outcome than triple therapy (RR, 1.15; 95%CI, 1.03-1.28; P<0.0001). Dual therapy was associated with significantly higher MI risk, insignificantly higher ST risk, and significantly lower major bleeding risk than triple therapy (RR1.23, 95%CI 1.01-1.49, P = 0.036; RR 1.43, 95 %CI 0.98-2.09, P = 0.064; and RR0.58, 95%CI 0.45-0.76, P<0.0001, respectively). Dual antithrombotic therapy was associated with higher ischemic risk but lower major bleeding risk than triple therapy. The data suggest that antithrombotic regimens should be based on tradeoffs between ischemia and bleeding risk.
Aging 2020
BACKGROUND:Recently, trimethylamine N-oxide (TMAO) unexplained gut microbe has been proposed as a promising risk factor for atherosclerotic cardiovascular disease (CVD) pathogenesis and adverse events. The relationship of TMAO with coronary atherosclerotic burden has been evaluated in patients with stable coronary artery disease and ST-segment elevation myocardial infarction, but still needs to be explored in newly diagnosed non-ST-segment elevation myocardial infarction (NSTEMI) patients.MATERIAL AND METHODS:A prospective, single-center, SZ-NSTEMI trial (ChiCTR1900022366) is underway to investigate the relationship of TMAO with the severity and prognosis of coronary atherosclerosis in newly diagnosed NSTEMI patients who will undergo coronary angiography with primary percutaneous coronary intervention (pPCI). The primary endpoint of the study will be assessed the association of TMAO with coronary atherosclerotic severity quantify by the number of diseased coronary arteries and SYNTAX score after the coronary angiography. The secondary endpoints will be identified the TMAO as a prognostic biomarker for the short (1 month) and long-term (12 months) major cardiovascular and cerebrovascular events (MACCEs) rate including myocardial infarction, target vessel revascularization, stroke, heart failure, all-cause rehospitalization, and all-cause mortality after the pPCI. The blood samples will be collected from each patient before the procedure to measure the TMAO by isotope dilution high-performance liquid chromatography. In conclusion, SZ-NSTEMI will be the first cohort that will be investigated the association of TMAO with the severity and prognosis of coronary atherosclerotic burden in NSTEMI patients, aiming to identify TMAO as a predictor and a prognostic biomarker.
Medicine 2020
China has the largest stroke population and at-risk population in the world. However, it has a lower thrombolytic therapy rate and longer onset-to-needle time/door-to-needle time for patients who had an acute stroke compared with developed countries, which might be due to redundant procedures or inefficient systems. Things are changing due to some new initiatives. Two years ago, a new emergency system in China, Stroke Emergency Map, was first launched as a regional emergency system in Shenzhen, the bustling metropolis just north of Hong Kong. As a result of the Stroke Emergency Map in Shenzhen, the number of thrombolytic cases increased in the last 2 years, from 568 to 809 annually. The Stroke Emergency Map, first pioneered in Shenzhen and now spreading to the rest of China, is a comprehensive and interdisciplinary system. The benefits are not just the immediate improvements in the acute stroke care because the continuous data collection and audit allows for improvements in logistics and future strategies.
Postgraduate medical journal 2019
Cardiac hypertrophy is characterized by an increase in myocyte size in the absence of cell division. This condition is thought to be an adaptive response to cardiac wall stress resulting from the enhanced cardiac afterload. The pathogenesis of heart dysfunction, which is one of the primary causes of morbidity and mortality in elderly people, is often associated with myocardial remodelling caused by cardiac hypertrophy. In order to well understand the potential mechanisms, we described the molecules involved in the development and progression of myocardial hypertrophy. Increasing evidence has indicated that micro-RNAs are involved in the pathogenesis of cardiac hypertrophy. In addition, molecular biomarkers including vascular endothelial growth factor B, NAD-dependent deacetylase sirtuin-3, growth/differentiation factor 15 and glycoprotein 130, also play important roles in the development of myocardial hypertrophy. Knowing the regulatory mechanisms of these biomarkers in the heart may help identify new molecular targets for the treatment of cardiac hypertrophy.
Journal of cellular and molecular medicine 2019
