Background People age at different rates. Biological age is a risk factor for many chronic diseases independent of chronological age. A good lifestyle is known to improve overall health, but its association with biological age is unclear. Methods This study included participants from the UK Biobank who had undergone 12-lead resting electrocardiography (ECG). Biological age was estimated by a deep learning model (defined as ECG-age), and the difference between ECG-age and chronological age was defined as Δage. Participants were further categorized into an ideal (score 4), intermediate (scores 2 and 3) or unfavorable lifestyle (score 0 or 1). Four lifestyle factors were investigated, including diet, alcohol consumption, physical activity, and smoking. Linear regression models were used to examine the association between lifestyle factors and Δage, and the models were adjusted for sex and chronological age. Results This study included 44,094 individuals (mean age 64 ± 8, 51.4% females). A significant correlation was observed between predicted biological age and chronological age (correlation coefficient = 0.54, P < 0.001) and the mean Δage (absolute error of biological age and chronological age) was 9.8 ± 7.4 years. Δage was significantly associated with all of the four lifestyle factors, with the effect size ranging from 0.41 ± 0.11 for the healthy diet to 2.37 ± 0.30 for non-smoking. Compared with an ideal lifestyle, an unfavorable lifestyle was associated with an average of 2.50 ± 0.29 years of older predicted ECG-age. Conclusion In this large contemporary population, a strong association was observed between all four studied healthy lifestyle factors and deaccelerated aging. Our study underscores the importance of a healthy lifestyle to reduce the burden of aging-related diseases.

Background/Aims: Myocardial infarction (MI) increases myocardial fibrosis (MF) and subsequent cardiac remodeling. Cholecystokinin octapeptide (CCK-8) is expressed in cardiomyocytes and plays an important role in cardiovascular regulation. In this study, we intend to use a rat model of myocardial infarction to evaluate the effects of CCK-8 on myocardial fibrosis and cardiac remodeling. Methods: Male Sprague-Dawley rats were separated into 3 groups: sham operation, MI + NaCl, and MI + CCK-8. All rats were subjected to left coronary artery ligation to induce MI or sham operation and then treated with CCK-8 or saline for 28 days. After 4 weeks, echocardiography was performed to assess cardiac function and myocardial fibrosis was evaluated using H&E and Masson's Trichrome-stained sections. The levels of BNP, CCK-8 in the plasma of all rats were detected by ELISA; RNA sequencing (RNA-seq) analysis was also adapted to detect differentially expressed genes in myocardial tissues of each group. Myocardial expression of fibrosis markers was analyzed by western blotting, immunohistochemistry and qRT-PCR. Results: CCK-8 was demonstrated to improve left ventricular function and results of H&E staining, Masson's trichrome staining, immunohistochemistry and western blotting showed that CCK-8 attenuated MF. Gene expression profiles of the left ventricles were analysed by RNA-seq and validated by qRT-PCR. Cardiac fibrosis genes were downregulated by CCK-8 in the left ventricle. Significance: CCK-8 can alleviate fibrosis in the noninfarcted regions and delay the left ventricular remodeling and the progress of heart failure in a MI rat model.

葡萄糖是心肌的重要能源物质之一,葡萄糖转运及代谢是心脏进行各项生物学活动的基础.Janus激酶-信号转导和转录通路(JAK-STAT)是一条由多种细胞因子参与的信号转导通路,几乎存在于机体的所有组织中.该文总结关于心肌葡萄糖代谢与JAK-STAT信号通路关系的文献发现,JAK-STAT信号转导通路通过多种方式参与胰岛素诱导的心肌葡萄糖代谢.

室性心律失常可导致血流动力学紊乱、心脏性猝死等恶性事件,已是医学界公认的事实,其复杂的发病机制、快速的病情进展、较高的病死率至今困扰临床医师。近年来,植入型心脏复律除颤器、射频消融术的应用已为许多患者带去福音,然而受技术水平、经济条件等诸多因素的限制,这些治疗手段在许多基层医院都无法实施。寻找一种操作简单、费用低、风险小、能够广泛开展的方法依然是医学工作者努力的方向。

As the morbidity and the mortality of acute myocardial infarction(AMI)in China are increasing rapidly,early biomarkers used for early diagnosisand treatment have become more and more important.The current major early biomarkers such as myoloperoxidas,C-reactive protein,matrix metallo-proteases,ischemiamodified albumin,heart-type fatty acid binding protein and cardiac troponin have important diagnostic value in AMI diagnosis and treatment.

Objective Beta blockers and angiotensin-converting enzyme inhibitors are known to attenuate the remodelling process in chronic heart failure, but the high mortality after heart failure must be resolved. We aimed to evaluate the effects of using high thoracic epidural sympathetic blockade (HTESB) as an adjunctive treatment to conventional therapy on the regression of left ventricular remodelling in chronic heart failure due to dilated cardiomyopathy.Methods We studied 40 patients with severe chronic heart failure due to dilated cardiomyopathy. These patients were randomly divided into two groups with equal size, and treated either by conventional therapy or HTESB as an adjunctive therapy (HTESB therapy) for 30 days. Echocardiography was performed before and after treatment.Results HTESB therapy was found to reduce left ventricular end-diastolic internal dimension by 5.3 mm, left atrial dimension by 7.6 mm, right ventricular dimension by 5.0 mm and right atrial dimension by 10.5 mm (P < 0.01). No discernable changes were observed in patients treated by conventional therapy. Moreover, HTESB therapy produced a greater increase in ejection fraction (11.2% vs. 2.2%) and more significant improvement to NYHA class than conventional therapy (P < 0.05).Conclusions These data demonstrate that the use of HTESB as an adjunctive therapy to conventional therapy in severe chronic heart failure due to dilated cardiomyopathy was associated with reduction in cardiac chamber dimension and increase in left ventricular systolic function. These beneficial effects on remodelling may lead to better prognosis.

Many complications may occur following acute myocardial infarction(AMI).Biomarkers can make effective prediction and monitoring about post AMI complications caused by pump failure,inflammation or unstable atherosclerosis plaque progression,such as heart failure,postmyocardial infarction syndrome,percutaneous coronary intervention or post thrombolytic reinfarction,etc..These biomarkers can be used as early diagnosis,active treatment,condition monitoring and treatment assessment after AMI.Here is to give a brief introduction about prognostic biomarkers of acute myocardial infarction,including B-type natriuretic peptide,ST2,adrenomedullin,copeptin,endothelin-1,creatine kinase isoenzyme,cardiac troponin,heart-type fatty acid binding protein,soluble CD40L,growth differentiation factor-15,C-reactive protein and so on.

Objective: Related transcriptional enhancer factor 1 (RTEF-1) is a key transcriptional regulator in endothelial function. In this study, we investigated a possible role for RTEF-1 in the regulation of microvascular relaxation and the underlying mechanism involved. Activation of fibroblast growth factor receptor 1 (FGFR1) by FGFs increases vasodilation, although transcriptional control of the molecular mechanisms underlying FGFR1 is still unclear. Materials and Methods: We demonstrated that RTEF-1 stimulated FGFR1 expression at the transcriptional level, specifically an area including Sp1 elements, as evidenced by promoter assays. Additionally, RTEF-1 increased FGFR1 mRNA and protein expression in vitro and in VE-cadherin-promoted RTEF-1 (VE-Cad/RTEF-1) transgenic mice, whereas RTEF-1 siRNA blocked the upregulation of FGFR1 expression. Furthermore, increased endothelial-dependent microvessel relaxation was observed in the coronary arteries of VE-Cad/RTEF-1 mice, and increased proliferation was observed in RTEF-1-overexpressing cells, both of which correlated to increased FGF/FGFR1 signaling and endothelial nitric oxide synthase (eNOS) upregulation. Our results indicate that RTEF-1 acts as a transcriptional stimulator of FGFR1 and is involved in FGF pathways by increasing microvessel dilatation via eNOS. Conclusions: These findings suggest that RTEF-1 plays an important role in FGFR1- stimulated vasodilatation. Understanding the effect of RTEF-1 in microvessel relaxation may provide beneficial knowledge in improving treatments in regards to ischemic vascular disorders.

Sudden cardiac death is a major reason for death after myocardial infarction.Most post-myocardial infarction patients at high risk of sudden cardiac death can be discovered by general inspection and thus death can be effectively prevented.This article examines the analysis of standard 12-lead electrocardiogram and its prediction of sudden cardiac death.

Acute myocardial infarction therapy involves two primary areas—pharmaceuticals and intervention.Intervention can quickly open the occlusive coronary artery,save the endangered myocardium and reduce the mortality of patients with acute myocardial infarction.When compared with interventional therapy,drug treatment was not only cheaper,but also easier in its application.This review examines advances in medications used in acute myocardial infarction.

Angiogenesis and apoptosis are reciprocal processes in endothelial cells. Bcl-2, an anti-apoptotic protein, has been found to have angiogenic activities. The purpose of this study was to determine the role of Bcl-2 in hypoxia-induced angiogenesis in endothelial cells and to investigate the underlying mechanisms. Human aortic endothelial cells (HAECs) were exposed to hypoxia followed by reoxygenation. Myocardial ischemia and reperfusion mouse model was used and Bcl-2 expression was assessed. Bcl-2 expression increased in a time-dependent manner in response to hypoxia from 2 to 72h. Peak expression occurred at 12h (3- to 4-fold, p<0.05). p38 inhibitor (SB203580) blocked hypoxia-induced Bcl-2 expression, whereas PKC, ERK1/2 and PI3K inhibitors did not. Knockdown of Bcl-2 resulted in decreased HAECs' proliferation and migration. Over-expression of Bcl-2 increased HAECs' tubule formation, whereas knockdown of Bcl-2 inhibited this process. In this model of myocardial ischemia and reperfusion, Bcl-2 expression was increased and was associated with increased p38 MAPK activation. Our results showed that hypoxia induces Bcl-2 expression in HAECs via p38 MAPK pathway.

Related transcriptional enhancer fictor-1 (RTEF-1) plays an important role in transcriptional regulation of angiogenic genes in hypoxic endothelial cells. The mechanisms involved in the induction of RTEF-1 expression in hypoxia are poorly understood. In bovine aortic endothelial cells (BAEC) subjected to hypoxia, Western blot and quantitative PCR analysis revealed that RTEF-1 protein and mRNA levels were significantly increased by hypoxia. To address the potential role of the hypoxia-inducible factor-1 (HIF-1) in RTFF-1 induction, a hepatoma cell line deficient in HIF-1 (c4) and a control HIF-1 positive cell line (vT{2}) were exposed to hypoxia. We report that RTEF-1 protein expression assessed by either Western blotting or immunofluorescence was increased in both cell lines. This demonstrates that HIF-1 is not required for RTEF-1 upregulation by hypoxia. Conversely, RTEF-1 appeared to regulate the expression of HIF-1: HIF-1 alpha promoter activity was increased (3.6-fold) by RTEF-1 overexpression in BAEC. Further-more, RTEF-1 enhanced BAEC proliferation and tubule formation; these were inhibited by RTEF-1 knockdown with siRNA. We propose that RTEF-1, acting via HIF-1, is a key regulator of angiogenesis ill response to hypoxia. (C) 2009 Elsevier Inc. All rights reserved.

Related transcriptional enhancer factor-1 (RTEF-1) plays an important role in transcriptional regulation of angiogenic genes in hypoxic endothelial cells. The mechanisms involved in the induction of RTEF-1 expression in hypoxia are poorly understood. In bovine aortic endothelial cells (BAEC) subjected to hypoxia, Western blot and quantitative PCR analysis revealed that RTEF-1 protein and mRNA levels were significantly increased by hypoxia. To address the potential role of the hypoxia-inducible factor-1 (HIF-1) in RTEF-1 induction, a hepatoma cell line deficient in HIF-1 (c4) and a control HIF-1 positive cell line (vT{2}) were exposed to hypoxia. We report that RTEF-1 protein expression assessed by either Western blotting or immunofluorescence was increased in both cell lines. This demonstrates that HIF-1 is not required for RTEF-1 upregulation by hypoxia. Conversely, RTEF-1 appeared to regulate the expression of HIF-1: HIF-1alpha promoter activity was increased (3.6-fold) by RTEF-1 overexpression in BAEC. Furthermore, RTEF-1 enhanced BAEC proliferation and tubule formation; these were inhibited by RTEF-1 knockdown with siRNA. We propose that RTEF-1, acting via HIF-1, is a key regulator of angiogenesis in response to hypoxia.

Fibroblast growth factor receptor-1 (FGFR-1) has been implicated in the process of cardiogenesis, although the underlying molecular mechanisms are poorly understood. In this study, we report the regulation of FGFR-1 expression by related transcriptional enhancer factor-1 (RTEF-1) in vitro (endothelial cells) and in vivo (RTEF-1 transgenic mice). FGFR-1 promoter activity, FGFR-1 mRNA and protein level Were Measured in bovine aortic endothelial cells (BAEC) in response to RTEF-1 and in endothelial cells isolated from livers in RTEF-1 transgenic mice. RTEF-1 stimulated FGFR-l promoter activity in a dose-dependent manner, RTEF-1 enhanced FGFR-1 mRNA (4-fold) and protein expression (3.5-fold) whereas RTEF-1 siRNA decreased FGFR-1 protein expression (4-fold). FGFR-1 mRNA and protein expression were also increased in endothelial cells isolated from livers of RTEF-1 transgenic mice. Furthermore, RTEF-1 enhanced tubule formation whereas this was decreased by RTEF-1 knockdown. Moreover, increased relaxation of microvessels was found in RTEF-1 transgenic mice compared to wild-type mice. Our results indicate that RTEF-1 acts as a transcriptional stimulator of FGFR-1 in endothelial cells through its activation of the FGFR-1 promoter, RTEF-1 thus plays ail important role in the regulation of FGFR-1 expression. These findings help further understand FGFR activity in angiogenesis and may lead to new therapeutic targets in ischemic vascular disorders. (C) 2009 Elsevier Inc. All rights reserved.

Background: Vascular endothelial growth factor (VEGF) is implicated in the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA) as well as atherosclerosis. The purpose of our study was: 1) to evaluate the expression of endothelial cell (EC) fibroblast growth factor 2 (FGF-2) and transforming growth factor beta 1 (TGF-beta 1) mRNA expression following vascular injury and VEGF modulation and 2) to assess whether VEGF indirectly stimulates smooth muscle cell (SMC) migration and proliferation via growth factors released by injured EC.Methods: Bovine aortic endothelial cells (BAEC) were cultured to near confluency and were serum starved. Linear wounds were made in medium with and without VEGF. FGF-2 and TGF-beta 1 mRNA expression were evaluated. Bovine aortic organ culture experiments were also carried out and growth factor expression was assessed. SMC proliferation and migration was assessed in response to EC injury medium with/without VEGF.Results: EC injury in the presence of VEGF increased FGF-2 mRNA. EC injury also induced TGF-beta 1 mRNA expression; however VEGF inhibited TGF-beta 1 mRNA expression in both injured and noninjured ECs. VEGF increased FGF-2 mRNA stability and did not alter TGF-beta 1 mRNA stability. SMC proliferation and migration was found to be induced by injured EC media and injury EC medium with VEGF, respectivelyConclusions: The results demonstrate that 1) VEGF indirectly stimulates SMC proliferation and migration through stimulation of the expression of FGF-2 and 2) VEGF inhibits the expression of TGF-beta\1 released by EC. Theses data further suggest an integral role for FGF-2 and TGF-beta 1 in wound repair. (c) 2008 Published by Elsevier Inc.

Fibroblast growth factor receptor-1 (FGFR-1) has been implicated in the process of cardiogenesis, although the underlying molecular mechanisms are poorly understood. In this study, we report the regulation of FGFR-1 expression by related transcriptional enhancer factor-1 (RTEF-1) in vitro (endothelial cells) and in vivo (RTEF-1 transgenic mice). FGFR-1 promoter activity, FGFR-1 mRNA and protein level were measured in bovine aortic endothelial cells (BAEC) in response to RTEF-1 and in endothelial cells isolated from livers in RTEF-1 transgenic mice. RTEF-1 stimulated FGFR-1 promoter activity in a dose-dependent manner. RTEF-1 enhanced FGFR-1 mRNA (4-fold) and protein expression (3.5-fold) whereas RTEF-1 siRNA decreased FGFR-1 protein expression (4-fold). FGFR-1 mRNA and protein expression were also increased in endothelial cells isolated from livers of RTEF-1 transgenic mice. Furthermore, RTEF-1 enhanced tubule formation whereas this was decreased by RTEF-1 knockdown. Moreover, increased relaxation of microvessels was found in RTEF-1 transgenic mice compared to wild-type mice. Our results indicate that RTEF-1 acts as a transcriptional stimulator of FGFR-1 in endothelial cells through its activation of the FGFR-1 promoter. RTEF-1 thus plays an important role in the regulation of FGFR-1 expression. These findings help further understand FGFR activity in angiogenesis and may lead to new therapeutic targets in ischemic vascular disorders.

Endothelial cell apoptosis plays a key role in the development of atherosclerosis.Many factors involved in atherosclerosis have an effect on endothelial cell apoptosis.Injury of the vascular endothelium increases endothelial cell apoptosis,consequently affecting vascular regulating and promoting the proliferation and migration of vascular smooth muscle cells and coagulation of blood.Therefore the injury of endothelium may initiate atherosclerosis.Research into endothelial cell apoptosis may help to understand the mechanisms of atherosclerosis.

Background: We have recently demonstrated that Related Transcription Enhancer Factor-1 (RTEF-1) is a transcription factor in endothelial cells. We also established that RTEF-1 regulated VEGF promot...