Although the pathogenesis of cardio-cerebrovascular disease (CCVD) is multifactorial, an increasing number of experimental and clinical studies have highlighted the importance of histone deacetylase (HDAC)-mediate...Although the pathogenesis of cardio-cerebrovascular disease (CCVD) is multifactorial, an increasing number of experimental and clinical studies have highlighted the importance of histone deacetylase (HDAC)-mediated epigenetic processes in the development of cardio-cerebrovascular injury. HDACs are a family of enzymes to balance the acetylation activities of histone acetyltransferases on chromatin remodeling and play essential roles in regulating gene transcription. To date, 18 mammalian HDACs are identified and grouped into four classes based on similarity to yeast orthologs. The zinc-dependent HDAC family currently consists of 11 members divided into three classes (class I, II, and IV) on the basis of structure, sequence homology, and domain organization. In comparison, class III HDACs (also known as the sirtuins) are composed of a family of NAD+-dependent protein-modifying enzymes related to the Sir2 gene. HDAC inhibitors are a group of compounds that block HDAC activities typically by binding to the zinc-containing catalytic domain of HDACs and have displayed an- ti-inflammatory and antifibrotic effects in the cardio-cerebrovascular system. In this review, we summarize the current knowledge about classifications, functions of HDACs and their roles and regulatory mechanisms in the cardio-cerebrovascular system. Pharmacological tar- geting of HDAC-mediated epigenetic processes may open new therapeutic avenues for the treatment of CCVD.展开更多
Background The benefit/risk ratio of stenting in acute ST-segment elevation myocardial infarction (STEMI) patients with single vessel intermediate stenosis culprit lesions merits further study, therefore the subject...Background The benefit/risk ratio of stenting in acute ST-segment elevation myocardial infarction (STEMI) patients with single vessel intermediate stenosis culprit lesions merits further study, therefore the subject of the present study. Methods and results It was a pro- spective, multicenter, randomized controlled trial. Between April 2012 and July 2015, 399 acute STEMI patients with single vessel disease and intermediate (40%-70%) stenosis of the culprit lesion before or after aspiration thrombectomy and/or intracoronary tirofiban (15 pg/kg) were enrolled and were randomly assigned (h 1) to stenting group (n = 201) and non-stenting group (n = 198). In stenting group, patients received pharmacologic therapy plus standard percutaneous coronary intervention (PCI) with stent implantation. In non-stenting group, pa- tients received pharmacologic therapy and PCI (thrombectomy), but without dilatation or stenting. Primary endpoint was 12-month rate of major adverse cardiac and eerebrovascular events (MACCE), a composite of cardiac death, non-fatal myocardial infarction (M1), repeat re- vascularization and stroke. Secondary endpoints were 12-month rates of all cause death, ischemia driven admission and bleeding complica- tion. Median follow-up time was 12.4 ~ 3.1 months. At 12 months, MACCE occurred in 8.0% of the patients in stenting group, as compared with 15.2% in the non-stenting group (adjusted HR: 0.42, 95% Ch 0.19-0.89, P = 0.02). The stenting group had lower non-fatal MI rate than non-stenting group, (1.5% vs. 5.5%, P = 0.03). The two groups shared similar cardiac death, repeat revascularization, stroke, all cause death, ischemia driven readmission and bleeding rates at 12 months. Conclusions Stent implantation had better efficacy and safety in reducing MACCE risks among acute STEMI patients with single vessel intermediate stenosis culprit lesions.展开更多
Coronary artery calcification (CAC) is highly prevalent in patients with coronary heart disease (CHD) and is associated with major adverse cardiovascular events. There are two recognized type of CAC--intimal and m...Coronary artery calcification (CAC) is highly prevalent in patients with coronary heart disease (CHD) and is associated with major adverse cardiovascular events. There are two recognized type of CAC--intimal and medial calcification, and each of them have specific risk factors. Several theories about the mechanism of vascular calcification have been put forward, and we currently believe that vascular calcification is an active, regulated process. CAC can usually be found in patients with severe CHD, and this asymptomatic phenomenon make early diagnosis of CAC important. Coronary computed tomographic angiography is the main noninvasive tool to detect calcified lesions. Measurement of coronary artery calcification by scoring is a reasonable metric for cardiovascular risk assessment in asymptomatic adults at intermediate risk. To date, effective medical treatment of CAC has not been identified. Several strategies of percutaneous coronary interven- tion have been applied to CHD patients with CAC, but with unsatisfactory results. Prognosis of CAC is still a major problem of CHD pa- tients. Thus, more details about the mechanisms of CAC need to be elucidated in order to improve the understanding and treatment of CAC.展开更多
基金This study was supported by grants from the National 973 Basic Research Program of China,the National Nature Science Foundation of China,Foundation of Program for New Century Excellent Talents in University (NCET-11-0311) to Yi F,Program for Changjiang Scholars and Innovative Research Team in University,the Special Financial Grant from the China Postdoctoral Science Foundation,the China Postdoctoral Science Foundation,the Shandong Province Post-doctoral Innovation Foundation
文摘Although the pathogenesis of cardio-cerebrovascular disease (CCVD) is multifactorial, an increasing number of experimental and clinical studies have highlighted the importance of histone deacetylase (HDAC)-mediated epigenetic processes in the development of cardio-cerebrovascular injury. HDACs are a family of enzymes to balance the acetylation activities of histone acetyltransferases on chromatin remodeling and play essential roles in regulating gene transcription. To date, 18 mammalian HDACs are identified and grouped into four classes based on similarity to yeast orthologs. The zinc-dependent HDAC family currently consists of 11 members divided into three classes (class I, II, and IV) on the basis of structure, sequence homology, and domain organization. In comparison, class III HDACs (also known as the sirtuins) are composed of a family of NAD+-dependent protein-modifying enzymes related to the Sir2 gene. HDAC inhibitors are a group of compounds that block HDAC activities typically by binding to the zinc-containing catalytic domain of HDACs and have displayed an- ti-inflammatory and antifibrotic effects in the cardio-cerebrovascular system. In this review, we summarize the current knowledge about classifications, functions of HDACs and their roles and regulatory mechanisms in the cardio-cerebrovascular system. Pharmacological tar- geting of HDAC-mediated epigenetic processes may open new therapeutic avenues for the treatment of CCVD.
文摘Background The benefit/risk ratio of stenting in acute ST-segment elevation myocardial infarction (STEMI) patients with single vessel intermediate stenosis culprit lesions merits further study, therefore the subject of the present study. Methods and results It was a pro- spective, multicenter, randomized controlled trial. Between April 2012 and July 2015, 399 acute STEMI patients with single vessel disease and intermediate (40%-70%) stenosis of the culprit lesion before or after aspiration thrombectomy and/or intracoronary tirofiban (15 pg/kg) were enrolled and were randomly assigned (h 1) to stenting group (n = 201) and non-stenting group (n = 198). In stenting group, patients received pharmacologic therapy plus standard percutaneous coronary intervention (PCI) with stent implantation. In non-stenting group, pa- tients received pharmacologic therapy and PCI (thrombectomy), but without dilatation or stenting. Primary endpoint was 12-month rate of major adverse cardiac and eerebrovascular events (MACCE), a composite of cardiac death, non-fatal myocardial infarction (M1), repeat re- vascularization and stroke. Secondary endpoints were 12-month rates of all cause death, ischemia driven admission and bleeding complica- tion. Median follow-up time was 12.4 ~ 3.1 months. At 12 months, MACCE occurred in 8.0% of the patients in stenting group, as compared with 15.2% in the non-stenting group (adjusted HR: 0.42, 95% Ch 0.19-0.89, P = 0.02). The stenting group had lower non-fatal MI rate than non-stenting group, (1.5% vs. 5.5%, P = 0.03). The two groups shared similar cardiac death, repeat revascularization, stroke, all cause death, ischemia driven readmission and bleeding rates at 12 months. Conclusions Stent implantation had better efficacy and safety in reducing MACCE risks among acute STEMI patients with single vessel intermediate stenosis culprit lesions.
基金This work were supported by the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (No. ZYLX201303), the National Natural Science Foundation of China (No. 81470429, No.81270285), and The capital health research and development of special (No 2011-2006-14).
文摘Coronary artery calcification (CAC) is highly prevalent in patients with coronary heart disease (CHD) and is associated with major adverse cardiovascular events. There are two recognized type of CAC--intimal and medial calcification, and each of them have specific risk factors. Several theories about the mechanism of vascular calcification have been put forward, and we currently believe that vascular calcification is an active, regulated process. CAC can usually be found in patients with severe CHD, and this asymptomatic phenomenon make early diagnosis of CAC important. Coronary computed tomographic angiography is the main noninvasive tool to detect calcified lesions. Measurement of coronary artery calcification by scoring is a reasonable metric for cardiovascular risk assessment in asymptomatic adults at intermediate risk. To date, effective medical treatment of CAC has not been identified. Several strategies of percutaneous coronary interven- tion have been applied to CHD patients with CAC, but with unsatisfactory results. Prognosis of CAC is still a major problem of CHD pa- tients. Thus, more details about the mechanisms of CAC need to be elucidated in order to improve the understanding and treatment of CAC.