冠状动脉造影正常的心绞痛患者血浆内皮素水平

运动试验阳性、冠状动脉（简称冠脉）造影无狭窄的心绞痛患者其心绞痛机制目前还不清楚，新近研究表明内皮功能不全引起的冠状动脉血管调节能力下降可能是其原因之一，许多内皮释放因子可能起一定作用。本研究的目的在于了解临床有心绞痛证据、冠脉造影正常患者血浆内皮素...     

VEGF在心血管疾病治疗中作用的研究进展

血管内皮细胞生长因子(VEGF)是目前最强有力的血管生成因子.VEGF和急性冠状动脉综合征的一些重要特征如血管内皮功能损伤和斑块内血管新生等密切相关,它在急性冠状动脉综合征中的变化对于判断急性冠状动脉综合征的发展、预后以及疗效可能具有重要意义,在包括冠心病在内的多种疾病涉及的生理病理性血管新生过程中起中心作用[1].     

冠心病患者血尿酸水平与血管内皮功能的相关性研究

目的分析冠心病患者血尿酸（UA）水平与血管内皮功能损伤的关系，从内皮功能损伤方面阐明UA水平升高是否为冠心病的独立危险因素。方法将冠心病患者分为稳定型心绞痛（SAP）组、不稳定型心绞痛（UAP）组、急性心肌梗死（AMI）组，并选健康对照（NC组），应用放免法测定血浆ET-1；硝酸还原酶法测定血浆NO；酶联免疫吸附双抗体夹心法测定血浆血管性血友病因子（vWF），尿酸还原酶法测定血UA，并分析其相关关系。结果与NC组比较，冠心病患者的UA、ET-1、vWF均显著增高（P〈0．01），NO显著降低（P〈0．01）；SAP组、UAP组、AMI组的UA水平与ET-1、vWF均显著正相关（P〈0．01），与NO呈显著负相关（P〈0．01），且随着病情的进展，相关性逐渐增强。结论UA水平越高，血管内皮损伤越重；UA水平升高可能通过引起血管内皮损伤和功能失调参与动脉粥样硬化过程，促进冠心病的发生及发展，UA水平升高是冠心病的独立危险因素。     

急性冠脉综合征患者经皮冠脉介入治疗前后血清hs-CRP和Fg的变化

急性冠脉综合征（ACS）主要包括不稳定型心绞痛（UAP）、急性心肌梗死（AMI）及心源性猝死，约占冠心病总数的30％。其发病机制主要是因为冠状动脉粥样斑块的炎症反应导致斑块不稳定、破裂、血管收缩和局部血栓形成，导致部分或全部血管阻塞。在冠状动脉粥样硬化（AS）的进展过程中有许多炎性细胞的参与，可以产生和释放细胞因子，促使肝细胞产生急性时相反应物，如C反应蛋白（CRP）。     

急性冠脉综合征与抑郁

抑郁在冠心病,尤其是急性冠脉综合征（ACS）患者中广泛而持续的存在。ACS后的抑郁不仅降低患者的生活质量，影响社会功能，增加医疗支出，并且是心脏事件和死亡率增加的独立危险因素。抑郁导致不良预后的机制包括：对治疗和生活方式调整的依从性差；植物神经功能紊乱；血小板活化；慢性炎症等。认知行为疗法和五羟色胺再摄取抑制剂（SSRI）用于治疗ACS后抑郁患者,具有良好的安全性和有效性．并显示改善预后的趋势。本文对ACS后抑郁的患病率、治疗,其对预后的影响及其产生影响的机制做一综述。     

脂联素与冠心病关系的研究现状及进展

冠状动脉粥样硬化性心脏病（冠心病）是严重危害人类健康的疾病，其发病率日益增高。大量实验研究证实．脂联素（APN）作为脂肪细胞分泌的一种脂肪因子，其通过抑制内皮细胞的炎症反应、巨噬细胞的功能及血管平滑肌细胞的增殖和迁移，发挥其对动脉粥样硬化的保护作用。临床研究表明，脂联素低浓度是冠状动脉狭窄及斑块不稳定的独立危险因素，其浓度也是冠心病患者未来主要心血管事件的一个预测因素。脂联素可能通过对原发性高血压（高血压）、高血脂、糖尿病、性别、吸烟等危险因素起作用来调控动脉粥样硬化的发生、发展。在药物治疗方面，噻唑类药物、血管紧张素转换酶抑制剂（ACEI）及血管紧张素受体阻断药（ARB）类药物、他汀类药物通过不同机制提升脂联素浓度．在冠心病治疗中发挥作用．     

血清胆红素水平与冠心病PCI术后再狭窄的研究进展

冠心病（CHD）目前仍然是影响人类生命健康的头号“杀手”，虽然冠脉介入治疗（PCI）及药物支架（DES）等技术的发展和应用极大的改善了冠心病患者的临床症状及生存质量，但是支架内再狭窄（ISR）限制了PCI的远期疗效，成为影响预后的主要因素 。ISR相关的因素复杂多样，其具体机制仍不明确，所以充分探讨冠心病PCI患者预后及再狭窄的相关影响因素已成为国内外研究的热点。有研究表明:吸烟、糖尿病史、脂蛋白a水平、总胆红素水平、支架直径、支架长度等因素与ISR的发生密切相关。有研究认为血清胆红素是冠状动脉支架内再狭窄的保护性因素，其水平与支架内再狭窄呈负相关，并且提出其可能的机制是胆红素的抗氧化自由基、抑制交感神经、保护血管内皮功能及抑制血小板的活化等作用。     

冠心病合并抑郁患者血管内皮功能、冠脉病变程度及病情稳定性的研究

目的探讨冠心病合并抑郁患者抑郁程度与肱动脉血管内皮功能、冠脉病变的严重程度及病情稳定性的关系。方法轻度抑郁组140例和中重度抑郁组128例,均接受冠脉造影和肱动脉超声检查。结果两组患者内皮依赖性血管舒张功能（FMD）和非内皮依赖性血管舒张功能（NMD）、冠状动脉Gensin i评分、病情稳定与不稳定的比例比较均有统计学差异（P均〈0.05）。结论中重度抑郁的冠心病患者血管内皮功能受损严重,冠状动脉严重狭窄,病情趋于不稳定。     

中青年人急性冠状动脉综合征的临床特点

目的 用回顾性分析探讨40岁以下（中青年组）急性冠状动脉综合征的临床表现及冠状动脉病变特点。方法 比较72例年龄小于40岁和276例年龄40岁及以上冠状动脉综合征病人的发病诱因、冠心病危险因素、选择性冠状动脉造影病变。结果中青年组ACS病人在发病前多数有过度劳累和精神紧张，大量吸烟占91.2％，明显高于40岁及以上病人（P＜0.01），高脂血症占73.6％，与中老年组差异无统计学意义。冠状脉造影结果显示，中青年组急性心肌梗死多为单支血管病变。合并心力衰竭和心源性休克以及病死率在中青年组均低于40岁及以上病人（P＜0.01）。结论 大量吸烟、过度劳累和精神刺激是中青年人冠状动脉综合征的常见诱因；吸烟、高脂血症、冠心病家族史是中青年急性心肌梗死病人的主要危险因素；中青年人冠状动脉以单支血管病变为主，预后较40岁及以上病人良好。     

血小板活化与冠心病

冠心病发病机制中血小板聚集和血栓形成学说日益引起广大学者的关注。目前,经皮冠状动脉介入术（PCI）已成为治疗冠心病的有效手段,然而临床实践已证明血小板活化状态明显影响PCI的效果。急性、亚急性血栓形成致血管再闭塞既是手术失败的主要原因,也是引起围手术期患者死亡等严重事件的关键因素。因此,探讨血小板活化在冠心病病程不同时期的作用,对于揭示冠心病的发病过程、介入治疗及预后判断等方面都具有重要意义。     

Endothelium-dependent and -independent functions are impaired in patients with coronary heart disease

Endothelium plays a pivotal role in the development of atherosclerosis. Endothelial dysfunction participates in the course of acute coronary event. Using high-resolution ultrasound technique, endothelial dysfunction has been demonstrated in patients with atherosclerosis and risk factors for coronary disease, such as hypertension, diabetes mellitus, hypercholesterolemia and being smokers. In the present study, using this non-invasive method, the endothelial function of the brachial artery of patients with coronary heart disease (CHD) (n = 71) and control subjects (n = 34) was investigated. The results showed that endothelium-dependent and -independent vasodilatation were impaired in patients with CHD (2.61+/-2.91 vs. 8.10+/-7.81%, 17.20+/-7.93 vs. 23.19+/-8.89%, respectively) (P<0.001). Flow-mediated dilation (FMD) was significantly positively correlated with nitroglycerine-induced dilation (P<0.001). On univariate and multivariate analysis, the extent of FMD was significantly correlated with serum HDL-C levels (P<0.01). In conclusion, our study indicates both endothelial and underlying smooth muscle functions were impaired in patients with CHD. Decreased HDL-C levels may impair endothelial function.     

冠心病患者血管内皮细胞功能的变化

目的　探讨血管内皮细胞功能障碍与冠心病 (CHD)的关系。方法　采用二维超声检测 70例CHD患者肱动脉血管内径 (内皮依赖性和内皮非依赖性舒缩功能 ) ,同时采用生化比色法测定CHD患者血浆一氧化氮 (NO) ,用放射免疫法测定血浆内皮素 (ET)、前列腺素 (PGI2 )、血栓素A2 (TXA2 )、肿瘤坏死因子 (TNF)、心钠素 (ANP)及降钙素基因相关肽 (CGRP)浓度 ,并以 2 0例健康人为对照组。结果　CHD组内皮依赖性血管舒缩功能与对照组比较明显降低 ,内皮非依赖性血管舒缩功能与对照组比较差异无显著性意义 ;CHD组与对照组比较 ,血浆平均ET、TXA2 、TNF显著升高 ,而血浆NO、PGI2 、ANP、CGRP水平显著降低。结论　内皮细胞功能障碍及其内皮源性血管活性物质和影响内皮功能的血管活性物质的失衡 ,在CHD的发病机制中起重要作用     

Endothelial function and coronary spastic angina

Coronary spasm plays an important role in the pathogenesis of not only variant angina but also coronary heart disease in general including acute coronary syndromes, especially in the Japanese population. The vascular endothelium has been reported to be a multifunctional organ whose integrity is essential for normal vascular physiology. Vascular endothelial dysfunction can be a critical factor in the pathogenesis of ischemic heart disease. Acetylcholine and methacholine cause vasodilation by endothelium-derived relaxing factor when the endothelium is functioning normally, whereas they cause vasoconstriction when the endothelium is removed or damaged. Coronary spasm can be induced by a variety of stimuli with different mechanisms of action, including acetylcholine and methacholine. Patients with coronary spasm may have a disturbance in endothelial function as well as local hyperreactivity of the coronary arteries.     

The Role of Asymmetric Dimethylarginine (ADMA) in Endothelial Dysfunction and Cardiovascular Disease

Endothelium plays a crucial role in the maintenance of vascular tone and structure. Endothelial dysfunction is known to precede overt coronary artery disease. A number of cardiovascular risk factors, as well as metabolic diseases and systemic or local inflammation cause endothelial dysfunction. Nitric oxide (NO) is one of the major endothelium derived vaso-active substances whose role is of prime importance in maintaining endothelial homeostasis. Low levels of NO are associated with impaired endothelial function. Asymmetric dimethylarginine (ADMA), an analogue of L-arginine, is a naturally occurring product of metabolism found in human circulation. Elevated levels of ADMA inhibit NO synthesis and therefore impair endothelial function and thus promote atherosclerosis. ADMA levels are increased in people with hypercholesterolemia, atherosclerosis, hypertension, chronic heart failure, diabetes mellitus and chronic renal failure. A number of studies have reported ADMA as a novel risk marker of cardiovascular disease. Increased levels of ADMA have been shown to be the strongest risk predictor, beyond traditional risk factors, of cardiovascular events and all-cause and cardiovascular mortality in people with coronary artery disease. Interventions such as treatment with L-arginine have been shown to improve endothelium-mediated vasodilatation in people with high ADMA levels. However the clinical utility of modifying circulating ADMA levels remains uncertain.     

Secondhand smoke exposure and cardiovascular disease

Exposure to secondhand tobacco smoke (SHS) is associated with an increased risk of coronary heart disease (CHD) among nonsmokers, which has been estimated to be 20% to 30%. SHS may also increase the risk of stroke; however, the link is equivocal compared with that for CHD. In addition, data from clinical and animal studies support the biologic plausibility of the association between SHS exposure and CHD. Recent experimental evidence has provided further insights into the pathophysiology of the cardiovascular damage associated with SHS exposure. Specifically, it has become clear that short-term, intense exposure to SHS may function as an important trigger of clinical manifestations of CHD via multiple mechanisms such as endothelial dysfunction, platelet activation, oxidative stress, inflammation, and alterations of the autonomic nervous system. This notion is further supported by recent studies suggesting that the risk of CHD associated with SHS exposure is likely to be reduced in the absence of high levels of recent exposure to SHS.     

Coronary endothelial cells: a target of ischemia reperfusion and its treatment?

Ischemia/reperfusion injury of the heart is not limited to cardiomyocytes but also extends to coronary vascular cells, and especially coronary endothelium. Indeed, in different animal models, ischemia followed by reperfusion (but not ischemia alone) markedly decreases endothelium-dependent relaxations of coronary arteries, and especially those induced by nitric oxide (NO), while endothelium-independent responses and smooth muscle responsiveness are usually maintained. Such injury to the endothelium appears to depend on the increased production of oxygen-derived free radicals upon reperfusion, leading to an increased degradation of NO and an acute inflammatory response characterized by an increased adhesion of neutrophils to endothelial cells. Indeed, reperfusion injury to the endothelium may be prevented by free radical scavengers, by prevention of adhesion and/or activation of neutrophils, by exogenous NO supply or increased endogenous production of NO, as well as by ischemic preconditioning. Given the essential role of the endothelium and of NO in the regulation of vasomotor tone, as well as platelet and leukocyte function, it is likely that such changes in coronary endothelial function have important adverse consequences in terms of altered perfusion, and increased risk of vasospasm, but also on the long-term risk of thrombosis and atherosclerosis. Although these coronary endothelial alterations have been essentially evaluated in experimental models and are indeed difficult to assess in the human coronary circulation in the context of myocardial infarction, data obtained in healthy volunteers demonstrate that such post-ischemic alterations of endothelial function may be detected in the peripheral circulation, with underlying molecular mechanisms similar to those demonstrated experimentally. A better understanding of the mechanisms responsible for such endothelial injury may lead to the development of new treatments that protect the endothelium during ischemia and reperfusion, but also possibly in other diseases associated with endothelial dysfunction.     

Endothelial dysfunction in human disease

The vascular endothelium plays a key role in the local regulation of vascular tone by the release of vasodilator substances (i.e. endothelium-derived relaxing factor (EDRF = nitric oxide, NO) and prostacyclin) and vasoconstrictor substances (i.e. thromboxane A2, free radicals, or endothelin). Using either agents like acetylcholine or changes in flow to stimulate the release of EDRF (NO), clinical studies have revealed the importance of EDRF in both basal and stimulated control of vascular tone in large epicardial coronary arteries and in the coronary microcirculation. The regulatory function of the endothelium is altered by cardiovascular risk factors or disorders such as hypercholesterolemia, chronic smoking, hypertension or chronic heart failure. Endothelial dysfunction appears to have detrimental functional consequences as well as adverse longterm effects, including vascular remodelling. Endothelial dysfunction is associated with impaired tissue perfusion particularly during stress and paradoxical vasoconstriction of large conduit vessels including the coronary arteries. These effects may cause or contribute to myocardial ischemia. Several mechanisms may be involved in the development of endothelial dysfunction, such as reduced synthesis and release of EDRF or enhanced inactivation of EDRF after its release from endothelial cells by radicals or oxidized low-density lipoprotein (LDL). Increased plasma levels of oxidized LDL have been noted in chronic smokers and are related to the extent endothelial dysfunction, raising the possibility that chronic smoking potentiates endothelial dysfunction by increasing circulating and tissue levels of oxidized LDL. In heart failure, cytokines and/or reduced flow (reflecting reduced shear stress) may be involved in the development of endothelial dysfunction and can be reversed by physical training. Other mechanisms include an activated renin-angiotensin system (i.e. postmyocardial infarction) with increased breakdown of bradykinin by enhanced angiotensin converting enzyme (ACE) activity. There is evidence that endogenous bradykinin is involved in coronary vasomotor control both in coronary conduit and resistance vessels. ACE inhibitors enhance endothelial function by a bradykinin-dependent mechanism and probably also by blunting the generation of superoxide anion. Endothelial dysfunction appears to be reversible by administering L-arginine, the precursor of nitric oxide, lowering cholesterol levels, physical training, antioxidants such as vitamin C, or ACE inhibition.     

Nitric oxide-mediated coronary flow regulation in patients with coronary artery disease: recent advances

Nitric oxide (NO) formed via endothelial NO synthase (eNOS) plays crucial roles in the regulation of coronary blood flow through vasodilatation and decreased vascular resistance, and in inhibition of platelet aggregation and adhesion, leading to the prevention of coronary circulatory failure, thrombosis, and atherosclerosis. Endothelial function is impaired by several pathogenic factors including smoking, chronic alcohol intake, hypercholesterolemia, obesity, hyperglycemia, and hypertension. The mechanisms underlying endothelial dysfunction include reduced NO synthase (NOS) expression and activity, decreased NO bioavailability, and increased production of oxygen radicals and endogenous NOS inhibitors. Atrial fibrillation appears to be a risk factor for endothelial dysfunction. Endothelial dysfunction is an important predictor of coronary artery disease (CAD) in humans. Penile erectile dysfunction, associated with impaired bioavailability of NO produced by eNOS and neuronal NOS, is also considered to be highly predictive of ischemic heart disease. There is evidence suggesting an important role of nitrergic innervation in coronary blood flow regulation. Prophylactic and therapeutic measures to eliminate pathogenic factors inducing endothelial and nitrergic nerve dysfunction would be quite important in preventing the genesis and development of CAD.     

Platelet-leukocyte-endothelial interactions in coronary artery disease.

It is generally recognized that formation of a platelet-fibrin-rich thrombus in an atherosclerotic coronary artery is the basis of unstable angina and acute myocardial infarction. Platelet hyperactivity has been identified in coronary risk factors such as hyperlipidemia and diabetes mellitus. Persistent activation of these cells results in release of growth factors that may contribute to the progression of atherosclerosis. Several recent studies show that endothelium, by generating or metabolizing a host of vasoactive substances, plays a critical role in the modulation of vascular tone. Important among these substances are prostacyclin (PGI2) and endothelium-derived relaxing factor (EDRF). The endothelium-dependent modulation of coronary artery tone correlates with the severity of atherosclerosis and the number of coronary risk factors. Procedures such as angioplasty and coronary bypass surgery injure the endothelium. The loss of endothelial smooth muscle relaxant function may contribute to the vasoconstriction and thrombosis often observed soon after these procedures. Thrombolysis (and subsequent reperfusion of the coronary artery) is also associated with severe endothelial dysfunction, with a resulting vasoconstrictor influence on the coronary vascular bed. Activation of leukocytes and their presence in the reperfused myocardium contribute to progression of myocardial injury by release of oxygen free radicals and proteolytic enzymes. Thus, it seems that a perturbation in this delicate equilibrium in cellular interactions relates to genesis and progression of myocardial ischemia.     

G-protein-coupled estrogen receptor as a new therapeutic target for treating coronary artery disease

Coronary heart disease(CHD) continues to be the greatest mortality risk factor in the developed world. Estrogens are recognized to have great therapeutic potential to treat CHD and other cardiovascular diseases; however,a significant array of potentially debilitating side effects continues to limit their use. Moreover,recent clinical trials have indicated that long-term postmenopausal estrogen therapy may actually be detrimental to cardiovascular health. An exciting new development is the finding that the more recently discovered G-protein-coupled estrogen receptor(GPER) is expressed in coronary arteries-both in coronary endothelium and in smooth muscle within the vascular wall. Accumulating evidence indicates that GPER activation dilates coronary arteries and can also inhibit the prolif-eration and migration of coronary smooth muscle cells. Thus,selective GPER activation has the potential to increase coronary blood flow and possibly limit the debilitating consequences of coronary atherosclerotic disease. This review will highlight what is currently known regarding the impact of GPER activation on coronary arteries and the potential signaling mechanisms stimulated by GPER agonists in these vessels. A thorough understanding of GPER function in coronary arteries may promote the development of new therapies that would help alleviate CHD,while limiting the potentially dangerous side effects of estrogen therapy.