Yanli Zhou

Exercise Training Protects Against Acute Myocardial Infarction via Improving Myocardial Energy Metabolism and Mitochondrial Biogenesis

Background/Aims: Acute myocardial infarction (AMI) represents a major cause of morbidity and mortality worldwide. Exercise has been proved to reduce myocardial ischemia-reperfusion (I/R) injury However it remains unclear whether, and (if so) how, exercise could protect against AMI. Methods: Mice were trained using a 3-week swimming protocol, and then subjected to left coronary artery (LCA) ligation, and finally sacrificed 24 h after AMI. Myocardial infarct size was examined with triphenyltetrazolium chloride staining. Cardiac apoptosis was determined by TUNEL staining. Mitochondria density was checked by Mito-Tracker immunofluorescent staining. Quantitative reverse transcription polymerase chain reactions and Western blotting were used to determine genes related to apoptosis, autophagy and myocardial energy metabolism. Results: Exercise training reduces myocardial infarct size and abolishes AMI-induced autophagy and apoptosis. AMI leads to a shift from fatty acid to glucose metabolism in the myocardium with a downregulation of PPAR-α and PPAR-γ. Also, AMI induces an adaptive increase of mitochondrial DNA replication and transcription in the acute phase of MI, accompanied by an activation of PGC-1α signaling. Exercise abolishes the derangement of myocardial glucose and lipid metabolism and further enhances the adaptive increase of mitochondrial biogenesis. Conclusion: Exercise training protects against AMI-induced acute cardiac injury through improving myocardial energy metabolism and enhancing the early adaptive change of mitochondrial biogenesis.

Non-coding RNAs in cardiac regeneration

Developing new therapeutic strategies which could enhance cardiomyocyte regenerative capacity is of significant clinical importance. Though promising, methods to promote cardiac regeneration have had limited success due to the weak regenerative capacity of the adult mammalian heart. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs, miRs) and long non-coding RNAs (lncRNAs), are functional RNA molecules without a protein coding function that have been reported to engage in cardiac regeneration and repair. In light of current regenerative strategies, the regulatory effects of ncRNAs can be categorized as follows: cardiac proliferation, cardiac differentiation, cardiac survival and cardiac reprogramming. miR-590, miR-199a, miR-17-92 cluster, miR302-367 cluster and miR-222 have been reported to promote cardiomyocyte proliferation while miR-1 and miR-133 suppress that. miR-499 and miR-1 promote the differentiation of cardiac progenitors into cardiomyocyte while miR-133 and H19 inhibit that. miR-21, miR-24, miR-221, miR-199a and miR-155 improve cardiac survival while miR-34a, miR-1 and miR-320 exhibit opposite effects. miR-1, miR-133, miR-208 and miR-499 are capable of reprogramming fibroblasts to cardiomyocyte-like cells and miR-284, miR-302, miR-93, miR-106b and lncRNA-ST8SIA3 are able to enhace cardiac reprogramming. Exploring non-coding RNA-based methods to enhance cardiac regeneration would be instrumental for devising new effective therapies against cardiovascular diseases.

Circulating miR-30d Predicts Survival in Patients with Acute Heart Failure

Background/Aims: Identification of novel biomarkers to identify acute heart failure (AHF) patients at high risk of mortality is an area of unmet clinical need. Recently, we reported that the baseline level of circulating miR-30d was associated with left ventricular remodeling in response to cardiac resynchronization therapy in advanced chronic heart failure patients. However, the role of circulating miR-30d as a prognostic marker of survival in patients with AHF has not been explored. Methods: Patients clinically diagnosed with AHF were enrolled and followed up for 1 year. Quantitative reverse transcription polymerase chain reactions were used to determine serum miR-30d levels. The univariate logistic regression analysis and multivariate logistic regression analysis were used to determine the predictors for all-cause mortality in AHF patients. Kaplan–Meier survival analysis was used to analyze the role of miR-30d in prediction of survival. Results: A total of 96 AHF patients were enrolled and followed up for 1 year. Serum miR-30d was significantly lower in AHF patients who expired in the one year follow-up period compared to those who survived. Univariate logistic regression analysis yielded 18 variables that were associated with all-cause mortality in AHF patients, while the multivariate logistic regression analysis identified 4 variables including heart rate, hemoglobin, serum sodium, and serum miR-30d level associated with mortality. ROC curve analysis showed that hemoglobin, heart rate and serum sodium displayed poor prognostic value for AHF (AUCs not higher than 0.700) compared to miR-30d level (AUC = 0.806). Kaplan–Meier survival analysis confirmed that patients with higher serum miR-30d levels had significantly lower mortality (P=0.001). Conclusion: In conclusion, this study shows evidence for the predictive value of circulating miR-30d as 1-year all-cause mortality in AHF patients. Large multicentre studies are further needed to validate our findings and accelerate the transition to clinical utilization.

Predictors of Long-Term Mortality in Patients With Acute Heart Failure

To investigate parameters which were related with long-term mortality in patients hospitalized for acute heart failure (AHF).A total of 287 patients with AHF presenting to the First Affiliated Hospital of Nanjing Medical University were enrolled into the registry from April 2012 to January 2015. The primary endpoint was all-cause mortality within 1 year; the association between variables and prognosis was assessed after 1 year.Among the 287 patients, 17 did not continue follow-up and 47 (17.4%) passed away. Baseline NT-proBNP and sST2 concentrations were higher amongst deceased than among survivors (P < 0.001). Serum sodium concentrations of patients who died were lower (P < 0.001). In receiver operator characteristics (ROC) analyses, the area under the curve (AUC) values for NT-proBNP, sST2, and serum sodium to predict 1-year mortality were 0.699 (95%CI 0.639-0.755), 0.692, (95%CI 0.634-0.747), and 0.694 (95%CI 0.634-0.750), respectively. The optimal cut-off points for NT-proBNP, sST2, and serum sodium were 2137.0 ng/L, 35.711 ng/mL, and 136.6 mmol/L, respectively. In Cox regression analysis, ln-transformed NT-proBNP (HR 1.546, P = 0.039), ln-transformed sST2 (HR1.542, P = 0.049), and serum sodium (HR 0.880, P = 0.000) values reliably predicted long-term mortality after multivariable adjustment.In patients with acute heart failure, NT-proBNP, sST2 and serum sodium are potential predictors of 1-year mortality.

Serum Irisin Predicts Mortality Risk in Acute Heart Failure Patients

Background/Aims: Irisin is a peptide hormone cleaved from a plasma membrane protein fibronectin type III domain containing protein 5 (FNDC5). Emerging studies have indicated association between serum irisin and many major chronic diseases including cardiovascular diseases. However, the role of serum irisin as a predictor for mortality risk in acute heart failure (AHF) patients is not clear. Methods: AHF patients were enrolled and serum was collected at the admission and all patients were followed up for 1 year. Enzyme-linked immunosorbent assay was used to measure serum irisin levels. To explore predictors for AHF mortality, the univariate and multivariate logistic regression analysis, and receiver-operator characteristic (ROC) curve analysis were used. To determine the role of serum irisin levels in predicting survival, Kaplan-Meier survival analysis was used. Results: In this study, 161 AHF patients were enrolled and serum irisin level was found to be significantly higher in patients deceased in 1-year follow-up. The univariate logistic regression analysis identified 18 variables associated with all-cause mortality in AHF patients, while the multivariate logistic regression analysis identified 2 variables namely blood urea nitrogen and serum irisin. ROC curve analysis indicated that blood urea nitrogen and the most commonly used biomarker, NT-pro-BNP, displayed poor prognostic value for AHF (AUCs ≤ 0.700) compared to serum irisin (AUC = 0.753). Kaplan-Meier survival analysis demonstrated that AHF patients with higher serum irisin had significantly higher mortality (P<0.001). Conclusion: Collectively, our study identified serum irisin as a predictive biomarker for 1-year all-cause mortality in AHF patients though large multicenter studies are highly needed.

Qiliqiangxin Attenuates Phenylephrine- Induced Cardiac Hypertrophy through Downregulation of MiR-199a-5p

Background/Aims: Qiliqiangxin (QL), a traditional Chinese medicine, has long been used to treat chronic heart failure. Previous studies demonstrated that QL could prevent cardiac remodeling and hypertrophy in response to hypertensive or ischemic stress. However, little is known about whether QL could modulate cardiac hypertrophy in vitro, and (if so) whether it is through modulation of specific hypertrophy-related microRNA. Methods: The primary neonatal rat ventricular cardiomyocytes were isolated, cultured, and treated with phenylephrine (PE, 50 µmol/L, 48 h) to induce hypertrophy in vitro, in the presence or absence of pretreatment with QL (0.5 µg/ml, 48 h). The cell surface area was determined by immunofluorescent staining for α-actinin. The mRNA levels of hypertrophic markers including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (MYH7) were assayed by qRT-PCRs. The protein synthesis of cardiomyocytes was determined by the protein/DNA ratio. The miR-199a-5p expression level was quantified in PE-treated cardiomyocytes and heart samples from acute myocardial infarction (AMI) mouse model. MiR-199a-5p overexpression was used to determine its role in the anti-hypertrophic effect of QL on cardiomyocytes. Results: PE induced obvious enlargement of cell surface in cardiomyocytes, paralleling with increased ANP, BNP, and MYH7 mRNA levels and elevated protein/DNA ratio. All these changes were reversed by the treatment with QL. Meanwhile, miR-199a-5p was increased in AMI mouse heart tissues. Of note, the increase of miR-199a-5p in PE-treated cardiomyocytes was reversed by the treatment with QL. Moreover, overexpression of miR-199a-5p abolished the anti-hypertrophic effect of QL on cardiomyocytes. Conclusion: QL prevents PE-induced cardiac hypertrophy. MiR-199a-5p is increased in cardiac hypertrophy, while reduced by treatment with QL. miR-199a-5p suppression is essential for the anti-hypertrophic effect of QL on cardiomyocytes.

Quality control of the blood pressure phenotype in the Gaoyou population study.

Abstract The Korotkoff approach is the only blood pressure (BP) measurement technique that allows contemporary data to be compared with decades of research. We randomly recruited 4483 people (53.3% women; mean age 52.1 years) from Gaoyou County, Jiangsu Province, China. Nine observers recorded the participants™ BP three times consecutively following Chinese Society of Hypertension guidelines. We assessed the BP phenotype based on five criteria: completeness of readings, percentage of identical BP readings, odd BP readings, end-digit preference and trends in BP from the first to the third reading. The proportion of participants with identical readings were 2.0% and 3.1% for systolic (SBP) and diastolic blood pressure (DBP), respectively. Among 26,898 BP values, 0.3% ended in an odd number. Among observers, the prevalence of identical readings varied from 0% to 5.3% for SBP and from 0% to 6.8% for DBP. Compared with the expected frequency of 20%, those ending in 0 had a lower frequency (17.2%; p < 0.001), whereas those ending in 8 had a higher frequency (22.4%; p < 0.001). From the first to the third measurement, SBP and DBP decreased (p < 0.001) by 0.87 and 0.55 mmHg, respectively. In conclusion, the procedures set up in the Gaoyou study produced a high-quality BP phenotype.

OS 14-07 PULSE WAVE VELOCITY COMPARED WITH MEAN ARTERIAL PRESSURE AND PULSE PRESSURE PROGNOSTIC IN THE POPULATION OF GAOYOU COUNTY, CHINA.

Objective: To evaluate the predictive value for cardiovascular disease incidence (CVD) of brachial-ankle pulse wave velocity (baPWV) based on a general Chinese population. Design and Method: The study group included 4251 participants with an average age of 52.1 ± 12.1 years and a mean baPWV of 14.8 ± 3.3 m/s. Cox regression was used to investigate the prognostic value of baPWV and forced the appropriate interaction term into the regression models to test the absolute risk associated with baPWV at different levels of mean arterial pressure. Results: Over a median follow-up of 4.4 years, the incidence of cardiovascular mortality, stroke and composite cardiovascular endpoints amounted to 21, 48 and 74. We adjusted for sex, age, body mass index, mean arterial pressure, waist-to-hip ratio, total cholesterol, current smoking, alcohol intake, blood glucose and use of antihypertensive drugs. With these adjustments, for each 1-SD increment in baPWV (3.23 m/s), the hazard ratios for an all-cause mortality, cardiovascular mortality, stroke or composite cardiovascular outcomes were 1.41(1.13–1.75), 1.68 (95% CI:1.20–2.35), 1.51 (95% CI:1.27–1.80), 1.57 (95% CI: 1.28–1.93), respectively. At any given level of mean arterial pressure (MAP), a higher baPWV was associated with a higher death rate. The area under curve (AUC) of baPWV was larger than pulse pressure in predicting composite cardiovascular events (Z = 2.45,P = 0.014). Conclusions: In conclusion, baPWV predicted a composite of cardiovascular outcomes above and beyond pulse pressure in a general Chinese population.

Hypertension related knowledge and behaviour associated with awareness, treatment and control of hypertension in a rural hypertensive population: a community based, cross-sectional survey

Abstract Background and objective: Hypertension-related knowledge and behaviour have been identified as influential factors associated with awareness, treatment and control of hypertension in urban regions. However, there were few studies on rural areas. This study aims to investigate whether hypertension related knowledge and behaviour were associated with hypertension awareness, treatment and control in Gaoyou, a rural area of Jiangsu province, China. Methods: A cross-sectional, population-based survey was conducted among hypertensive individuals in rural areas of Gaoyou, the south-eastern of China in 2010. We identified 1943 subjects with hypertension among 4536 subjects participated in this study and collected information about medical history, use of medication, hypertension related knowledge and behaviour by a standardized questionnaire. Results: This study showed that 41.07% of subjects were aware of their disease, 30.01% of subjects were taking antihypertensive medication and 5.04% of subjects controlled their blood pressure. Multivariate logistic regression analysis showed that subjects who knew the threshold, the lifelong treatment of hypertension and measured blood pressure at least once a year had better detection, treatment or control of hypertension. Conclusion: Hypertension related knowledge and behaviour were associated with awareness, treatment and control rate of hypertension in the rural areas of south-eastern China.