长链非编码RNA在心律失常中的作用研究进展

长链非编码RNA(lncRNA)在心律失常中具有重要作用.lncRNA通过影响心脏电重构、结构重构、能量代谢障碍及自主神经重构等机制参与房颤的发生,通过调节离子通道编码基因诱发长QT间期综合征,通过改变心脏传导影响心肌肥厚/心力衰竭诱导的心律失常等.本文综述上述研究进展,以期为心律失常的研究和治疗提供新思路.     

心肌肥厚：calcineurin-NFAT通路可能是新的治疗靶点

通常所说的心肌肥厚指病理性心肌重构（remodeling）,从不同角度的分类包括结构性重构、功能性重构、生化重构及电生理重构等.一般认为,心肌肥厚是心肌对压力负荷、体积负荷、肌小节蛋白变异或心梗后心肌收缩力下降等的代偿性反应,目的是使左心室室壁压力正常化,维持正常的心脏泵血功能,阻止心脏衰竭的发生和发展.随着研究的深入进行,一项多中心回顾性流行病学调查发现,与原来的实验预期相反,心肌肥厚与心脏病的高死亡率密切相关,是心衰和恶性心律失常发生的主要因素.……     

左心室肥厚逆转的药物治疗近况

左心室肥厚(LVH)是心脏对慢性压力和容量负荷过重的适应性反应,以心脏的质量、形状,心肌数量和质量以及室壁细胞排列发生改变为特征的心室重构,是高血压的常见并发症。长期左心室肥厚可引起心肌缺血,最终致心力衰竭和心律失常。防止和逆转左室肥厚是高血压治疗的一个重要目标,也是评价降压药物疗效的重要指标。     

依那普利和牛磺酸逆转肾性高血压大鼠左心室肥厚及抗心律失常的作用

肾性高血压大鼠形成左心室肥厚后,心肌线粒体Ca2+含量和用成串电脉冲刺激离体心脏引起的心律失常发生率显著增高。依那普利(6mg·kg^-1),牛磺酸(30mg·kg^-1)在左心室肥厚形成后(术后第9周)开始连续po给药9周,均能显著降低血压、左心室重与体重的比值、电刺激引起的心律失常发生率和心肌线粒体Ca²⁺含量,且两药合用后,降压作用增强。本实验表明,肾性高血压左心室肥厚大鼠的心脏对电刺激的敏感性增加,更容易产生心律失常;依那普利和牛磺酸对肾性高血压大鼠有降压、逆转左心室肥厚的作用,并能降低左心室肥厚大鼠的心脏对电刺激的敏感性。     

心梗后心室重构与RAS

急性心梗(Acute Myocardial Infarction,AMI)后心室重构是心脏事件重要的独立危险因素,与心律失常、猝死、心力衰竭等密切相关.AMI后心脏血流动力学改变伴随神经一内分泌异常、心室肥厚、心腔扩大的过程即为心室重构.     

卡托普利和辛伐他汀联用在心肌纤维化中的疗效观察

心肌纤维化(myocardial fibrosis,MF)是病毒性心肌炎(viral mvocarditis,VM)特征性病理变化,表现为胶原的合成与降解失衡,间质中胶原沉积增多,各型胶原比例失调,心脏顺应性下降,僵硬度增加等特征,过度的心肌纤维化是病毒性心肌炎发生心律失常、心力衰竭、心脏性猝死等并发症的决定因素[1].心肌纤维化是多种心脏疾病发展到一定阶段的共同病理改变,是心肌重构的主要表现之一,可致心肌僵硬度增加、心室舒张功能减退、冠状动脉储备下降,甚至引起猝死[2].     

依那普利和牛磺酸逆转肾性高血压大鼠左心室肥厚及抗心律失常的作用

肾性高血压大鼠形成左心室肥厚后，心肌线粒体Ｃａ２＋含量和用成串电脉冲刺激离体心脏引起的心律失常发生率显著增高。依那普刊（６ｍｇ·ｋｇ－１），牛磺酸（３０ｍｇ·ｋｇ－１）在左心室肥厚形成后（术后第９周）开始连续ｐｏ给药９周，均能显著降低血压、左心室重与体重的比值、电刺激引起的心律失常发生率和心肌线粒体Ｃａ２＋含量，且两药合用后，降压作用增强，本实验表明，肾性高血压左心室肥厚大鼠的心脏对电刺激的敏感性增加．更容易产生心律失常；依那普利和牛磺酸对肾性高血压大鼠有降压、逆转左心室肥厚的作用，并能降低左心室肥厚大鼠的心脏对电刺激的敏感性。     

TGF-β/Smads信号通路在心肌纤维化发生和治疗中应用前景的研究进展

心肌纤维化(MF)是多种心脏疾病发展到一定阶段的共同病理改变,是心肌重构的主要表现之一。这种病理变化存在于多种心血管疾病中,与心律失常、心力衰竭等疾病密切相关。转化生长因子-β(TGF-β)在MF的发生和发展中起着重要作用。TGF-β/Smads信号通路是TGF-β发挥生物学作用的主要通路,其分子组成与分子调节复杂,现将它在MF发生和治疗中应用前景作一综述。     

心肌纤维化的分子机制--粘附

心肌纤维化在心肌重塑中起着重要作用,与高血压所致的左室肥厚、心梗后心室重构和心衰心脏球形改变密切相关[1]。心肌纤维化对心功能损害表现在以下几个方面。首先,心肌细胞间质纤维化使室壁僵硬度增加,心肌顺应性减低,导致心脏舒张功能受损[2,3],第二,细胞外基质(ECM)和成纤维细     

抗高血压药物治疗心肌肥厚的研究进展

<正> 心肌肥厚广泛见于高血压心脏病和肺源性心脏病等多种心脏疾患。心肌肥厚是心脏对抗增高的压力负荷(室壁应力增加)以维持心脏泵功能,是心脏受累的病理表现。过去对左心室肥厚(LVH)未予以重视。经多年实践研究,已逐渐认识到高血压心脏的向心性肥厚常伴心肌舒张功能不良即顺应性降低,冠脉灌注不足,心肌缺血,导致心脏舒缩功能均障碍,近年的前瞻性研究证实LVH是一极重要的诊断及预后     

Modulation of cardiovascular remodeling with statins: fact or fiction?

The concept of cardiac remodeling implies a complex mixture of myocardial ischemia, and increased wall stress that results in molecular, cellular and interstitial changes in the heart. Clinically, cardiac remodeling is manifested as a change in size, shape and function of the heart. Morphologically the key feature of remodeling is myocyte hypertrophy, myocyte loss from necrosis or apoptosis, as well as interstitial cell growth especially fibroblast proliferation leading to myocardial fibrosis. Cardiac remodeling is influenced by hemodynamic load, neurohumoral activation, and other factors that can further affect the remodeling process. Despite advances in the management of heart failure, morbidity and mortality still present major health care issues in these patients. Statins (HMG Coenzyme A reductase inhibitors) play a key role in the management of ischemic heart disease. Recent studies indicate that statins may modulate cardiac remodeling by affecting signals that cause fibroblast growth, and myocyte hypertrophy and loss. In this paper we review the mechanisms of cardiac remodeling and the mechanisms of potential beneficial effects of statins on cardiac remodeling.     

EGCG Blocked Phenylephrin-Induced Hypertrophy in H9C2 Cardiomyocytes,by Activating AMPK-Dependent Pathway

AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism. Previous studies have shown that activation of AMPK results in suppression of cardiac myocyte hypertrophy via inhibition of the p70S6 kinase (p70S6K) and eukaryotic elongation factor-2 (eEF2) signaling pathways. Epigallocatechin-3-gallate (EGCG), the major polyphenol found in green tea, possesses multiple protective effects on the cardiovascular system including cardiac hypertrophy. However, the molecular mechanisms has not been well investigated. In this study, we found that EGCG could significantly reduce natriuretic peptides type A (Nppa), brain natriuretic polypeptide (BNP) mRNA expression and decrease cell surface area in H9C2 cardiomyocytes stimulated with phenylephrine (PE). Moreover, we showed that AMPK is activated in H9C2 cardiomyocytes by EGCG, and AMPK-dependent pathway participates in the inhibitory effects of EGCG on cardiac hypertrophy. Taken together, our findings provide the first evidence that the effect of EGCG against cardiac hypertrophy may be attributed to its activation on AMPK-dependent signaling pathway, suggesting the therapeutic potential of EGCG on the prevention of cardiac remodeling in patients with pressure overload hypertrophy.     

Signal transduction in cardiac hypertrophy--dissecting compensatory versus pathological pathways utilizing a transgenic approach.

Targeted and regulated genetic manipulation, physiological intervention to introduce biomechanical stress and injury, sophisticated measurement of cardiac function in transgenic heart at whole organ and cellular level, and the molecular/biochemical/genomic analysis of signaling pathways in cardiomyocytes represent the most significant advances in recent years in this field. Such progress has helped make inroads into understanding the molecular mechanism of cardiac hypertrophy and heart failure. Delineating intracellular signaling pathways involved in the different aspects of cardiac hypertrophy and remodeling will have significant implications in drug development for heart failure.     

冬虫夏草对肾性高血压大鼠血管重构的影响

目的 :观察冬虫夏草对肾性高血压大鼠心肌肥厚、血管重构的影响。方法 :体重为 160～ 180 g健康雄性 Wistar大鼠随机分为对照组、高血压组及治疗组 ,于术后第 10天大鼠灌胃 (ig)冬虫夏草煎剂 2 ml,每日两次 (bid) ,连续 2 0天 ,观察冬虫夏草对心肌肥厚、血管重构的影响。结果 :冬虫夏草明显改善高血压大鼠血压、心肌肥厚及血管重构。结论 :冬虫夏草对肾性高血压有治疗作用。     

高血压病患者左室构型及功能变化与室性心律失常的关系

目的探讨高血压病患者左室构型及功能变化与室性心律失常的关系.方法采用超声多谱勒技术检测154例高血压病患者左室构型及功能,并结合24小时动态心电图检测.结果各构型组舒张功能均有不同程度的改变,向心性肥厚及离心性肥厚型组收缩功能明显降低,其室性早搏(VA),复杂VA及室性心动过速(VT)检出率均明显高于正常构型及向心性重构型.结论高血压病左室肥厚构型及功能变化与室性心律失常有明显关系.     

I(f) in non-pacemaker cells: role and pharmacological implications.

Pacemaker channels play a major role in the generation of sinoatrial rhythmic activity. However, their expression is not confined to specialized myocardial cells, such as primary and subsidiary pacemakers. Electrophysiological and molecular data collected over the last ten years have demonstrated that f-channels are also present in non-pacemaker cardiomyocytes, and become upregulated in cardiac hypertrophy and failure. Mislocalized expression and/or overexpression of f-channels are a consequence of electrophysiological remodeling and, from a clinical point of view, may represent an arrhythmogenic mechanism in heart failure, a condition associated with a high risk for sudden cardiac death. The potential arrhythmogenic role of I(f) and the availability of selective f-channel blockers cause I(f) to be a suitable therapeutic target in heart disease.     

Oral administration of alcalase potato protein hydrolysate‐APPH attenuates high fat diet‐induced cardiac complications via TGF‐β/GSN axis in aging rats

Consumption of high fat diet (HFD) is associated with increased cardiovascular risk factors among elderly people. Aging and obesity induced‐cardiac remodeling includes hypertrophy and fibrosis. Gelsolin (GSN) induces cardiac hypertrophy and TGF‐β, a key cytokine, which induces fibrosis. The relationship between TGF‐β and GSN in aging induced cardiac remodeling is still unknown. We evaluated the expressions of TGF‐β and GSN in HFD fed 22 months old aging SD rats, followed by the administration of either probucol or alcalase potato protein hydrolysate (APPH). Western blotting and Masson trichrome staining showed that APPH (45 and 75 mg/kg/day) and probucol (500 mg/kg/day) treatments significantly reduced the aging and HFD‐induced hypertrophy and fibrosis. Echocardiograph showed that the performance of the hearts was improved in APPH, and probucol treated HFD aging rats. Serum from all rats was collected and H9c2 cells were cultured with collected serums separately. The GSN dependent hypertrophy was inhibited with an exogenous TGF‐β in H9c2 cells cultured in HFD+ APPH treated serum. Thus, we propose that along with its role in cardiac fibrosis, TGF‐β also acts as an upstream activator of GSN dependent hypertrophy. Hence, TGF‐β in serum could be a promising therapeutic target for cardiac remodeling in aging and/or obese subjects.     

A central role of EGF receptor transactivation in angiotensin II -induced cardiac hypertrophy

In addition to their physiological roles in the cardiovascular system (CVS), G-protein-coupled receptor (GPCR) agonists such as noradrenaline, endothelin-1 and angiotensin II (Ang II) are known to be involved in the development of cardiac hypertrophy. Recent studies using targeted overexpression of the angiotensin AT(1) receptor in cardiomyocytes suggest that Ang II can directly promote the growth of cardiomyocytes via transactivation of the epidermal growth factor (EGF) receptor and subsequent activation of mitogen-activated protein kinases (MAPKs). This process is mediated by the production of heparin-binding EGF (HB-EGF) by metalloproteases. Blockade of the generation of HB-EGF by metalloprotease inhibitors, or abrogation of EGF receptor kinase activity by selective pharmacological inhibitors or antisense oligonucleotides, protects against Ang II-mediated cardiac hypertrophy. These approaches offer a potential therapeutic strategy to prevent cardiac remodeling and hypertrophy, and possibly prevent progression to heart failure.