巨噬细胞极化在心血管疾病中的作用

心血管病,尤其是急性心肌梗死和收缩性心功能衰竭已成为西方国家患者死亡的主要原因,在发展中国家也呈明显上升趋势.缺血性的心脏病已经成为普遍现象,是引起病人死亡的主要原因.尽管早期血管再建和药物治疗能够明显提高心肌梗死后的生存率,但仍有大量病人发展成心力衰竭.巨噬细胞除了具有免疫防御和维持组织稳态功能,还在心肌梗死诱导的病理生理过程中发挥重要作用.巨噬细胞的亚群已被证实参与心血管疾病(动脉粥样硬化、心肌梗死、心肌缺血、心肌纤维化)的发生和发展,在心脏损伤和心肌重塑中有重要作用,研究基于巨噬细胞调控治疗心血管疾病的治疗策略很有价值.     

饱和氢盐水对大鼠心肌缺血再灌注损伤致炎性细胞因子的影响

急性心肌梗死目前主要还是集中在溶栓、介入治疗和冠状动脉旁路移植术方面,但这些治疗面临心肌缺血后再灌注引起的损伤.炎性反应在心肌梗死及缺血再灌注损伤可引起血管内皮损伤、心肌微循环障碍、组织再灌注不良及白细胞浸润心肌等,最终会导致心肌细胞凋亡,心功能损伤.近期研究发现氢气通过抗感染、抗氧化损伤、减轻凋亡等机制对心血管疾病具有治疗作用[1],并可以减轻心肌缺血再灌注诱发的心肌功能障碍及细胞凋亡.本实验探讨炎性因子在饱和氢盐水治疗大鼠心肌缺血再灌注损伤中的作用.     

干细胞移植在心血管疾病治疗中的应用进展

心血管疾病,已成为人类死亡的主要疾病,干细胞移植为心血管疾病的治疗带来了新的希望.细胞移植为病损心脏细胞重建及衰竭心脏功能恢复提供了一种全新的治疗方法.干细胞具有自我更新、定向分化成为心肌细胞等多种组织细胞的潜能.其增殖分化能力能维持终身,目前可供移植的种子细胞包括胚胎干细胞,骨骼肌生肌细胞,骨髓干细胞,内皮祖细胞等,移植避免了免疫排斥和伦理道德问题.近期研究表明移植的干细胞能在心肌损伤部位中存活,增强心功能.     

Sirt3在心肌梗死中的作用研究进展

心肌梗死是一种严重的心血管疾病,其会导致心肌能量代谢的紊乱。Sirt3作为一种重要的线粒体去乙酰化酶,在心肌梗死后的能量代谢调节中发挥重要作用。本综述旨在分析和总结Sirt3在心肌梗死后能量代谢调节中的研究进展,以期为心血管疾病的治疗提供新的理论和实践依据。     

骨髓间充质干细胞治疗心肌梗死

心肌梗死是导致人类死亡的主要疾病之一,干细胞移植为心肌梗死的治疗提供了一种新的思路,因而成为近年来研究的热点。骨髓间充质干细胞因为不涉及伦理道德问题,而且取材方便,所以具有较好的临床应用前景。近年来有关骨髓间充质干细胞向心肌细胞分化的研究,骨髓间充质干细胞的输送方式及移行机制,移植细胞对心功能的影响以及移植转基因干细胞的治疗前景的研究有了长足的进展。     

心肌再生途径的研究

急性心肌梗死（AMI）已成全球缺血性心血管疾病的主要死因之一。近年来,随着经皮冠状动脉介入治疗和再灌注时间的改善,急性心梗患者死亡率显著降低。但心肌梗死后导致心肌细胞数量减少,纤维瘢痕增生,引起心室结构重建、心肌弹性下降、脏壁扩张变薄和心功能下降等,逐渐形成慢性心力衰竭（CHF）。结合我国人口老龄化及冠心病发病的特点,意味着更多的人会逐渐发展形成CHF,将严重影响患者的预后及生活质量。心肌再生是让受损心肌周围细胞和血管再次增殖分化,从而减轻心室结构重建,改善心功能。本文就促心肌再生方法,包括信号通路调节、干细胞移植治疗、心脏重编码、外泌体旁分泌刺激、新兴组织工程做一综述。     

骨髓间充质干细胞移植治疗心血管疾病的临床研究新进展

自2001年骨髓干细胞被首次用于治疗心肌梗死以来,干细胞移植治疗心血管疾病的临床研究已历经了10余年。近年来,BMSC因其可塑性、遗传稳定性和免疫耐受性而成为用于心肌修复较为理想的细胞。本文主要对BMSC移植治疗心血管疾病的临床研究的现状和进展加以综述。     

单核/巨噬细胞调控心梗后心肌纤维化的研究进展

正急性心肌梗死(acute myocardial infarction,AMI)是一种严重的缺血性心脏病,持续的心肌缺血可导致心肌细胞大量凋亡或坏死而丢失。心肌纤维化(myocardial fibrosis,MF)是指在心肌的正常组织结构中胶原纤维过量积聚、心脏组织中胶原浓度显著升高或胶原成分发生激剧改变,导致心脏僵硬度增加、心功能下降。MF是心肌梗死的主要病理生理学过程,可导致心脏重构(cardiac remodeling),并逐渐发展为慢性心力衰竭(chronic heart failure,CHF)~([1])。     

87例急性心肌梗死的临床护理体会

心肌梗死是由于冠状动脉血液循环突然停止，导致心肌发生严重且持久的缺血坏死性改变的一组症候群。急性心肌梗死（AMI）是冠心病的严重类型，近年来发病逐渐增多，已成为影响公众健康的主要问题，急性心肌梗死（AMI）是在冠状动脉病变的基础上，发生冠状动脉血供急剧减少或中断，使相应的心肌严重而持久地急性缺血导致心肌坏死，     

miRNA与急性心肌梗死

心肌梗死是心血管疾病导致死亡的最主要原因之一。miRNA是一类非编码小分子RNA。研究证实，发生急性心肌梗死后miRNA表达异常，通过转录后水平参与MI及其并发症的病理生理过程，有望成为急性心肌梗死新的生化标志物和治疗靶点。在下文中，我们首先对急性心肌梗死的发病机制进行了简要阐述，然后对miRNA和急性心肌梗死的相关性进行全面论述。     

Combining aspirin with angiotensin converting enzyme inhibitors in heart failure: how safe is it?

The above discussion on the interaction of aspirin and ACE inhibitors seems to suggest that aspirin in high doses may have adverse interaction with ACE inhibitors in patients with heart failure but the data obtained is not sufficient or conclusive to recommended omission of aspirin in patients with heart failure. This raises a query in the mind of the physician whether to use a combination or not? The role of aspirin in the early period after myocardial infarction is well established so is the role of ACE inhibitors. Hence in patients with myocardial infarction and preserved left ventricular function it would not be wrong to administer combination of ACE inhibitors and aspirin. Albeit at a lower dose. In patients with large myocardial infarction or heart failure, warfarin may be an option but still needs to be documented in large trials. As suggested long term use of aspirin after infarction is still ambiguous and may be harmful in patients with heart failure with its anticedent side effects. But long term benefits of ACE inhibitors in heart failure are well documented. Hence if a choice has to be made whether to discontinue either of the two drugs it would be preferable to stop the aspirin. To answer the issue of use of aspirin in patients with heart failure it would be essential to conduct a double blind randomized trial comparing known anti-thrombotic treatment, aspirin and anti-coagulants on mortality in patients with heart failure, especially caused by coronary artery disease. Such a trial is underway at the present and till the results are available it should be left to clinical judgement of the physician whether to administer aspirin in patients with heart failure after weighing the benefits versus risk.     

The effects of acetylcholinesterase inhibitors on the heart in acute myocardial infarction and heart failure: From cells to patient reports

Cardiovascular diseases remain a major cause of morbidity and mortality worldwide. Cardiovascular diseases such as acute myocardial infarction, ischaemia/reperfusion injury and heart failure are associated with cardiac autonomic imbalance characterized by sympathetic overactivity and parasympathetic withdrawal from the heart. Increased parasympathetic activity by electrical vagal nerve stimulation has been shown to provide beneficial effects in the case of cardiovascular diseases in both animals and patients by improving autonomic function, cardiac remodelling and mitochondrial function. However, clinical limitations for electrical vagal nerve stimulation exist because of its invasive nature, costly equipment and limited clinical validation. Therefore, novel therapeutic approaches which moderate parasympathetic activities could be beneficial for in the case of cardiovascular disease. Acetylcholinesterase inhibitors inhibit acetylcholinesterase and hence increase cholinergic transmission. Recent studies have reported that acetylcholinesterase inhibitors improve autonomic function and cardiac function in cardiovascular disease models. Despite its potential clinical benefits for cardiovascular disease patients, the role of acetylcholinesterase inhibitors in acute myocardial infarction and heart failure remediation remains unclear. This article comprehensively reviews the effects of acetylcholinesterase inhibitors on the heart in acute myocardial infarction and heart failure scenarios from in vitro and in vivo studies to clinical reports. The mechanisms involved are also discussed in this review.     

Plasma brain natriuretic peptide levels in coronary heart disease with preserved systolic function

We evaluated the circulating levels of brain natriuretic peptide (BNP) in stable angina, unstable angina, and myocardial infarction relating hormone levels to extension of coronary disease and number of vessels involved after angiographic examination. We studied 86 patients consecutively undergoing angiographic coronary examination and echocardiographic evaluation for coronary heart disease. These included 15 control subjects (group 0), 21 with stable angina (group I), 26 with unstable angina (group II), and 24 with non-Q myocardial infarction (group III). Patients with heart failure, a history of myocardial infarction, or recent myocardial damage with electrocardiographic S-T elevation were excluded. BNP levels in patients with unstable angina and myocardial infarction were significantly increased with respect to the group with stable angina (P<0.01). There were no differences between the groups with unstable angina and myocardial infarction. Analysis of peptide levels in relation to the number of involved vessels demonstrated a significant increase in patients with three-vessel disease compared with subjects with one or two vessels involved (P<0.03); among subjects with mono-vessel disease, patients with left descendent anterior stenosis had a more-marked BNP elevation than subjects with stenosis in other regions (P<0.01). Hence, BNP levels appear to be elevated in coronary disease, especially in acute coronary syndromes, even in the absence of systolic dysfunction. BNP levels also seem to be related to the severity of coronary atherosclerosis and number of vessels involved. BNP could prove a novel marker for risk stratification, not only in heart failure but also in coronary heart disease.     

Activation and release of degradative proteinases within the myocardium are the trigger for ventricular remodeling in chronic heart failure

Our conceptual framework of chronic heart failure is based upon the neurohormonal model. In this construct, neurohormonal systems that provide short-term homeostasis remain activated after a myocardial injury, producing progressive ventricular dysfunction and worsening heart failure. However, this model fails to explain several aspects of the pathophysiology of heart failure, including the mechanisms that trigger neurohoromone release and those that lead to ventricular dysfunction in the absence of a large myocardial infarction. These gaps in our understanding can be explained by an expanded model of heart failure, which focuses on myocardial matrix events as the triggers for disease progression. This model embraces the neurohormonal model, and integrates the roles of the immune system and the myocardial fibroblast, within the matrix, to more fully describe the initiation and progression of the disease.     

Plasma brain natriuretic peptide levels in coronary heart disease with preserved systolic function

Abstract. We evaluated the circulating levels of brain natriuretic peptide (BNP) in stable angina, unstable angina, and myocardial infarction relating hormone levels to extension of coronary disease and number of vessels involved after angiographic examination. We studied 86 patients consecutively undergoing angiographic coronary examination and echocardiographic evaluation for coronary heart disease. These included 15 control subjects (group 0), 21 with stable angina (group I), 26 with unstable angina (group II), and 24 with non-Q myocardial infarction (group III). Patients with heart failure, a history of myocardial infarction, or recent myocardial damage with electrocardiographic S-T elevation were excluded. BNP levels in patients with unstable angina and myocardial infarction were significantly increased with respect to the group with stable angina (P<0.01). There were no differences between the groups with unstable angina and myocardial infarction. Analysis of peptide levels in relation to the number of involved vessels demonstrated a significant increase in patients with three-vessel disease compared with subjects with one or two vessels involved (P<0.03); among subjects with mono-vessel disease, patients with left descendent anterior stenosis had a moremarked BNP elevation than subjects with stenosis in other regions (P<0.01). Hence, BNP levels appear to be elevated in coronary disease, especially in acute coronary syndromes, even in the absence of systolic dysfunction. BNP levels also seem to be related to the severity of coronary atherosclerosis and number of vessels involved. BNP could prove a novel marker for risk stratification, not only in heart failure but also in coronary heart disease.     

Chemokine receptor (CCR2) genotype is associated with myocardial infarction and heart failure in patients under 65 years of age

Inflammation is associated with atherosclerosis of coronary arteries. Chemokines have an important role in inflammation. The CCR2 chemokine receptor mediates leukocyte chemoattraction, which is involved in the pathogenesis of coronary heart disease. We prospectively studied 1960 consecutive patients aged under 65 years and referred for a first-time left ventricular catheter. Left heart catheters were analyzed by two independent cardiologists for the presence of myocardial infarction (regional wall motion abnormality) and moderate or severely reduced left ventricular function on cineventriculography and presence of coronary atherosclerosis on angiography. Genotyping for CCR2 V64I polymorphism was performed. The presence of the rare allele of the CCR2 gene was significantly associated with a higher prevalence of myocardial infarction on cinventriculography (32.0% vs. 24.2%, moderately or severely reduced left ventricular function (14.0% vs. 9.5%) and NYHA class III or IV (16.7% vs. 12.2%). The association of the CCR2 genotype with heart failure was not independent of the presence of myocardial infarction in multivariate analysis. There was no association of the CCR2 genotype with coronary atherosclerosis. The CCR2 genotype seems to predispose patients for myocardial infarction before the age of 65 years. The higher prevalence of heart failure in gene carriers with the rare alle might be a consequence of myocardial infarction. If the CCR2 genotype is associated with higher mortality in the general population must be investigated in further studies.     

Development of an Experimental Model of Cardiac Failure Combined with Type I Diabetes Mellitus

The doses and mode of streptozotocin injection for modeling heart failure combined with type 1 diabetes mellitus have been determined. Combined disease was induced in animals by injecting the selected streptozotocin dose (60 mg/kg intraperitoneally) at the stage of heart failure formation (2 weeks after coronary occlusion). This protocol of experiment led to development of hyperglycemia, body weight loss, and formation of myocardial cicatrix and hypertrophy corresponding to signs of heart failure paralleled by diabetes mellitus.     

A growing role for the Hippo signaling pathway in the heart

Heart disease is a major cause of clinical morbidity and mortality, and a significant health and economic burden worldwide. The loss of functional cardiomyocytes, often a result of myocardial infarction, leads to impaired cardiac output and ultimately heart failure. Therefore, efforts to improve cardiomyocyte viability and stimulate cardiomyocyte proliferation remain attractive therapeutic goals. Originally identified in Drosophila, the Hippo signaling pathway is highly conserved from flies to humans and regulates organ size through modulation of both cell survival and proliferation. This is particularly relevant to the heart, an organ with limited regenerative ability. Recent work has demonstrated a critical role for this signaling cascade in determining heart development, homeostasis, injury and the potential for regeneration. Here we review the function of canonical and non-canonical Hippo signaling in cardiomyocytes, with a particular focus on proliferation and survival, and how this impacts the stressed adult heart.     

Intermedin attenuates myocardial infarction through activation of autophagy in a rat model of ischemic heart failure via both cAMP and MAPK/ERK1/2 pathways

Intermedin is a proopiomelanocortin-derived peptide before opioid promoting cortical hormone, its main function embodies in mononuclear macrophages and neutrophilic granulocytes to inhibit the proinflammatory cytokines. The aim of this study is to determine intermedin attenuates myocardial infarction and its related mechanisms in a rat model of ischemic heart failure. After rat model of ischemic heart failure was set up, myocardial infarction, blood levels of activities of creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) were effectively reduced by treatment with intermedin. Tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) in a rat model of ischemic heart failure were recovered by pretreatment with intermedin. Administrate of intermedin availably promoted cAMP contents and suppressed caspase-3 protein in ischemic heart failure rat. ERK1/2 and LC3 protein expression were significantly activated and autophagy was significantly promoted by intermedin in a rat model of ischemic heart failure. These results indicate that intermedin protected rat heart, attenuates myocardial infarction from ischemic heart failure in the rat model. The underlying mechanisms may include upregulation of cAMP, ERK1/2 and LC3 protein expression and activating of autophagy.