Oxidative stress in atherogenesis and arterial thrombosis: the disconnect between cellular studies and clinical outcomes.

Atherosclerosis is a multifactorial disease for which the molecular etiology of many of the risk factors is still unknown. As no single genetic marker or test accurately predicts cardiovascular death, phenotyping for markers of inflammation may identify the individuals at risk for vascular diseases. Reactive oxygen species (ROS) are key mediators of signaling pathways that underlie vascular inflammation in atherogenesis, starting from the initiation of fatty streak development through lesion progression to ultimate plaque rupture. Various animal models of atherosclerosis support the notion that ROS released from NAD(P)H oxidases, xanthine oxidase, lipoxygenases, and enhanced ROS production from dysfunctional mitochondrial respiratory chain indeed have a causatory role in atherosclerosis and other vascular diseases. Human investigations also support the oxidative stress hypothesis of atherogenesis. This is further supported by the observed impairment of vascular function and enhanced atherogenesis in animal models that have deficiencies in antioxidant enzymes. The importance of oxidative stress in atherosclerosis is further emphasized because of its role as a unifying mechanism across many vascular diseases. The main contraindicator for the role oxidative stress plays in atherosclerosis is the lack of effectiveness of antioxidants in reducing primary endpoints of cardiovascular death and morbidity. However, this lack of effectiveness by itself does not negate the existence or causatory role of oxidative stress in vascular disease. Lack of proven markers of oxidative stress, which could help to identify a subset of population that can benefit from antioxidant supplementation, and the complexity and subcellular localization of redox reactions, are among the factors responsible for the mixed outcomes in the use of antioxidants for the prevention of cardiovascular diseases. To better understand the role of oxidative stress in vascular diseases, future studies should be aimed at using advances in mouse and human genetics to define oxidative stress phenotypes and link phenotype with genotype.     

Pathophysiologic cardiovascular changes in stress and depression

Fear, anger, and grief may precipitate myocardial ischemia and infarction. The prognosis of patients with inducible ischemia during mental stress is worse than in those without inducible ischemia. The sympathetic nervous system plays an important role in stress-associated changes in cardiovascular regulation and contributes to cardiovascular morbidity and mortality by inducing vasoconstriction and tachycardia, as well as arrhythmia. Hostility--previously termed type A personality--is often associated with sympathetic hyperreactivity to mental stress and carries an increased risk for atherosclerotic vascular disease. As endothelial dysfunction is an early manifestation of atherosclerosis, the impact of mental stress on endothelial function is also important. Acute mental stress induces prolonged endothelial dysfunction in healthy volunteers, which is prevented by selective endothelin A receptor antagonism. This represents an important link between mental stress and atherosclerotic vascular disease. In addition, patients with depression show hypercortisolemia, and changes in platelet function leading to a prothrombotic state. These findings help to explain the increased cardiovascular risk in patients with depression.     

ROCKs as therapeutic targets in cardiovascular diseases

There is growing evidence that Rho-kinases (ROCKs), the immediate downstream targets of the small guanosine triphosphate-binding protein Rho, may contribute to cardiovascular disease. ROCKs play a central role in diverse cellular functions such as smooth muscle contraction, stress fiber formation and cell migration and proliferation. Overactivity of ROCKs is observed in cerebral ischemia, coronary vasospasm, hypertension, vascular inflammation, arteriosclerosis and atherosclerosis. ROCKs, therefore, may be an important and still relatively unexplored therapeutic target in cardiovascular disease. Recent experimental and clinical studies using ROCK inhibitors such as Y-27632 and fasudil have revealed a critical role of ROCKs in embryonic development, inflammation and oncogenesis. This review will focus on the potential role of ROCKs in cellular functions and discuss the prospects of ROCK inhibitors as emerging therapy for cardiovascular diseases.     

ROCKs as therapeutic targets in cardiovascular diseases

There is growing evidence that Rho-kinases (ROCKs), the immediate downstream targets of the small guanosine triphosphate-binding protein Rho, may contribute to cardiovascular disease. ROCKs play a central role in diverse cellular functions such as smooth muscle contraction, stress fiber formation and cell migration and proliferation. Overactivity of ROCKs is observed in cerebral ischemia, coronary vasospasm, hypertension, vascular inflammation, arteriosclerosis and atherosclerosis. ROCKs, therefore, may be an important and still relatively unexplored therapeutic target in cardiovascular disease. Recent experimental and clinical studies using ROCK inhibitors such as Y-27632 and fasudil have revealed a critical role of ROCKs in embryonic development, inflammation and oncogenesis. This review will focus on the potential role of ROCKs in cellular functions and discuss the prospects of ROCK inhibitors as emerging therapy for cardiovascular diseases.     

Mental Stress and Its Effects on Vascular Health

Coronary artery disease continues to be a major cause of morbidity and mortality despite significant advances in risk stratification and management. This has prompted the search for alternative nonconventional risk factors that may provide novel therapeutic targets. Psychosocial stress, or mental stress, has emerged as an important risk factor implicated in a higher incidence of cardiovascular events, and although our understanding of this far ranging and interesting phenomenon has developed greatly over recent times, there is still much to be learned regarding how to measure mental stress and how it may impact physical health. With the current coronavirus disease 2019 global pandemic and its incumbent lockdowns and social distancing, understanding the potentially harmful biological effects of stress related to life-changing events and social isolation has become even more important. In the current review our multidisciplinary team discusses stress from a psychosocial perspective and aims to define psychological stress as rigorously as possible; discuss the pathophysiologic mechanisms by which stress may mediate cardiovascular disease, with a particular focus to its effects on vascular health; outline existing methods and approaches to quantify stress by means of a vascular biomarker; outline the mechanisms whereby psychosocial stressors may have their pathologic effects ultimately transduced to the vasculature through the neuroendocrine immunologic axis; highlight areas for improvement to refine existing approaches in clinical research when studying the consequences of psychological stress on cardiovascular health; and discuss evidence-based therapies directed at reducing the deleterious effects of mental stress including those that target endothelial dysfunction. To this end we searched PubMed and Google Scholar to identify studies evaluating the relationship between mental or psychosocial stress and cardiovascular disease with a particular focus on vascular health. Search terms included “myocardial ischemia,” “coronary artery disease,” “mental stress,” “psychological stress,” “mental1 stress1,” “psychologic1 stress1,” and “cardiovascular disease1.” The search was limited to studies published in English in peer-reviewed journals between 1990 and the present day. To identify potential studies not captured by our database search strategy, we also searched studies listed in the bibliography of relevant publications and reviews.     

基于北京血管健康分级指导的智能化全生命周期心脏和血管健康管理

心血管疾病的传统诊疗模式面对庞大的代谢相关心血管疾病群体已显示其局限性。在2015版基础上最新修订的北京血管健康分级系统是实现全生命周期管理心脏和血管健康和智能化辅助改善心血管疾病预后的基础。传统的心血管疾病终末期诊治的模式将被这一新型健康管理模式所取代，使"治未病"的理念得以实施，构建全科医学参与的涵盖看护照料、养老康复与发病后诊疗一体化和规范化的服务系统，使影响我国人口健康最大的慢病群体——血管相关疾病患者的负担在人工智能＋互联网＋5G的应用下得到前所未有的控制，助力健康中国梦想。     

The effect of self-efficacy on cardiovascular lifestyle

Background

It is important that patients with vascular diseases adopt a healthy lifestyle so as to reduce vascular risk. Since self-efficacy is an important precondition for health behavior change in patients with chronic disease, we investigated whether self-efficacy was associated with cardiovascular lifestyle in patients with clinical manifestations of vascular diseases.

Methods and design

In this observational cohort study, 125 patients who had recently been referred for cerebrovascular disease, coronary heart disease, or peripheral arterial disease participated in a 1-year self-management intervention. They completed a self-efficacy questionnaire and questions about their cardiovascular lifestyle at baseline and after 1 year. Logistic regression analyses were performed to quantify the impact of change in self-efficacy on physical activity, smoking behavior, alcohol consumption, and food choices.

Results

Improved self-efficacy was associated with improved adherence to guidelines for physical activity (OR 3.5, 95%CI 1.0–11.0) and food choices (B 0.15, 95%CI 0.00–0.31). No such improvement was seen regarding adherence to guidelines for smoking or alcohol intake.

Conclusion

In patients with vascular diseases, improvements in self-efficacy are associated with an improvement in cardiovascular lifestyle, namely, more exercise and better food choices.     

Bewegung im Alter

Physical activity in old age is important as lack of physical activity can promote obesity. However, cardiovascular diseases, such as coronary artery disease, valvular diseases, heart failure and peripheral artery disease, potentially limit the capability to undertake physical activity in the elderly. It is of importance to identify these patients concerned and to refer them to a specialist in terms of appropriate diagnostics and therapy. Clinical and therapeutic aspects of (cardio)vascular diseases which limit physical activity are discussed.     

Vasoactive peptides in cardiovascular (patho)physiology

Numerous vasoactive agents play an important physiological role in regulating vascular tone, reactivity and structure. In pathological conditions, alterations in the regulation of vasoactive peptides result in endothelial dysfunction, vascular remodeling and vascular inflammation, which are important processes underlying vascular damage in cardiovascular disease. Among the many vasoactive agents implicated in vascular (patho)biology, angiotensin II (Ang II), endothelin (ET), serotonin and natriuretic peptides appear to be particularly important because of their many pleiotropic actions and because they have been identified as potential therapeutic targets in cardiovascular disease. Ang II, ET-1, serotonin and natriuretic peptides mediate effects via specific receptors, which belong to the group of G-protein-coupled receptors. ET, serotonin and Ang II are primarily vasoconstrictors with growth-promoting actions, whereas natriuretic peptides, specifically atrial, brain and C-type natriuretic peptides, are vasodilators with natriuretic effects. Inhibition of vasoconstrictor actions with drugs that block peptide receptors, compounds that inhibit enzymes that generate vasoactive peptides or agents that increase levels of natriuretic peptides are potentially valuable therapeutic tools in the management of cardiovascular diseases. This review focuses on ET, natriuretic peptides and serotonin. The properties and distribution of these vasoactive agents and their receptors, mechanisms of action and implications in cardiovascular (patho)physiology will be discussed.     

BNP等指标在心血管疾病诊疗中的临床意义

目的探讨脑钠肽(BNP)、尿酸(UA)、乳酸脱氢酶(LDH)和肌钙蛋白T(TnT)检查指标在心血管疾病诊断及预后观察中的作用。方法选取心血管疾病患者271例和非心血管疾病患者271例分别作为心血管疾病组和对照组,并将心血管疾病组按照民族类型进一步分为维吾尔族心血管疾病组和汉族心血管疾病组,检测所有研究对象BNP、LDH、UA和TnT水平,对检测结果进行统计分析。结果心血管疾病组BNP、UA、LDH和TnT水平明显高于对照组,差异有统计学意义(P0.05);维吾尔族心血管疾病组LDH、TnT水平高于汉族心血管疾病组,汉族心血管疾病组BNP、UA水平高于维吾尔族心血管疾病组,差异均无统计学意义(P0.05);心力衰竭、冠心病患者治疗1周后BNP水平下降最明显,且与治疗前比较差异有统计学意义(P0.05);心力衰竭患者治疗1周后UA水平与治疗前比较差异有统计学意义(P0.05)。结论 BNP、UA、LDH和TnT联合检测在心血管疾病的早期诊断、治疗及预后观察中有重大临床意义。     

Vasoactive peptides in cardiovascular (patho)physiology

Numerous vasoactive agents play an important physiological role in regulating vascular tone, reactivity and structure. In pathological conditions, alterations in the regulation of vasoactive peptides result in endothelial dysfunction, vascular remodeling and vascular inflammation, which are important processes underlying vascular damage in cardiovascular disease. Among the many vasoactive agents implicated in vascular (patho)biology, angiotensin II (Ang II), endothelin (ET), serotonin and natriuretic peptides appear to be particularly important because of their many pleiotropic actions and because they have been identified as potential therapeutic targets in cardiovascular disease. Ang II, ET-1, serotonin and natriuretic peptides mediate effects via specific receptors, which belong to the group of G-protein-coupled receptors. ET, serotonin and Ang II are primarily vasoconstrictors with growth-promoting actions, whereas natriuretic peptides, specifically atrial, brain and C-type natriuretic peptides, are vasodilators with natriuretic effects. Inhibition of vasoconstrictor actions with drugs that block peptide receptors, compounds that inhibit enzymes that generate vasoactive peptides or agents that increase levels of natriuretic peptides are potentially valuable therapeutic tools in the management of cardiovascular diseases. This review focuses on ET, natriuretic peptides and serotonin. The properties and distribution of these vasoactive agents and their receptors, mechanisms of action and implications in cardiovascular (patho)physiology will be discussed.     

Cysteinyl cathepsins and mast cell proteases in the pathogenesis and therapeutics of cardiovascular diseases

The initiation and progression of cardiovascular diseases involve extensive arterial wall matrix protein degradation. Proteases are essential to these pathological events. Recent discoveries suggest that proteases do more than catabolize matrix proteins. During the pathogenesis of atherosclerosis, abdominal aortic aneuryms, and associated complications, cysteinyl cathepsins and mast cell tryptases and chymases participate importantly in vascular cell apoptosis, foam cell formation, matrix protein gene expression, and pro-enzyme, latent cytokine, chemokine, and growth factor activation. Experimental animal disease models have been invaluable in examining each of these protease functions. Deficiency and pharmacological inhibition of cathepsins or mast cell proteases have allowed their in vivo evaluation in the setting of pathological conditions. Recent discoveries of highly selective and potent inhibitors of cathepsins, chymase, and tryptase, and their applications in vascular diseases in animal models and non-vascular diseases in human trials, have led to the hypothesis that selective inhibition of cathepsins, chymases, and tryptase will benefit patients suffering from cardiovascular diseases. This review highlights recent discoveries from in vitro cell-based studies to experimental animal cardiovascular disease models, from protease knockout mice to treatments with recently developed selective and potent protease inhibitors, and from patients with cathepsin-associated non-vascular diseases to those affected by cardiovascular complications.     

Running for health: how much running for how much health?

Increasing physical activity has been shown to reduce physiological markers of cardiovascular disease, such as high blood pressure, vascular endothelial cell reactivity and arterial stiffness. In this issue of Clinical Science, H?gg and colleagues have chosen the spontaneously hypertensive rat model to investigate the effect of exercise on vascular function. They found that spontaneous running increased aortic compliance and antioxidant capacity with decreased oxidative stress in mesenteric arteries, presenting support for the cardiovascular protective effects of physical activity. Two important aspects of their study include the magnitude of the running stimulus and the choice of artery to evaluate.     

骨髓间充质干细胞在心血管疾病中的研究及应用

背景：骨髓间充质干细胞具有多向分化潜能,对肝脏疾病、神经系统疾病、肺脏疾病、肾脏疾病的治疗都显示出其优越性,对心血管疾病治疗的研究也日益增多。目的：对骨髓间充质干细胞在心血管疾病中的应用以及治疗心血管疾病的机制进行综述。方法：应用计算机检索CNKI和Pubmed数据库中1985年1月至2009年12月关于骨髓间充质干细胞治疗心血管疾病的文章,在标题和摘要中以＂骨髓间充质干细胞,细胞移植,治疗,心血管疾病＂或＂bone marrow mesenchymal stem cells,cells transplant,therapy,cardiovascular disease＂为检索词进行检索,最终纳入42篇文献进行综述。结果与结论：众多的研究表明骨髓间充质干细胞可以在梗死的心肌中分化形成有功能活性的心肌、血管内皮等组织,改善心脏的功能,干细胞移植在治疗心血管疾病方面已表现出传统治疗方法所无可比拟的优越性。     

基于血管平滑肌视角的牵张应力对血管重构影响的研究进展

血管重构（vascular remodeling）是众多心血管疾病发生发展的始动因素和最终归宿。动脉粥样硬化、高血压、肺动脉高压及冠状动脉支架植入均可引起不同程度的血管重构。牵张应力（stretch stress）是由搏动血流产生的作用于血管壁的一种生物机械力,异常的牵张应力作用于血管平滑肌细胞（vascular smooth muscle cells, VSMCs）可引起动脉硬化、冠脉支架内再狭窄等一系列事件。因此,本文旨在从血管平滑肌细胞的角度就牵张应力对血管重构的影响作一综述。     

Application of pharmacogenomics in the prevention of diabetic cardiovascular disease: mechanistic basis and clinical evidence for utilization of the haptoglobin genotype in determining benefit from antioxidant therapy

Atherosclerotic cardiovascular disease (CVD) and diabetic vascular disease have been associated with an increase in oxidative stress. Mechanistic studies in vitro and in animals have demonstrated a direct role for oxidatively modified protein and lipid molecules in the pathophysiology of these diseases. As a result of this oxidation hypothesis numerous studies have been carried out over the past 5-10 years testing the ability of antioxidant vitamins to decrease the incidence of these diseases. The general consensus from these studies, involving over 200,000 individuals, has been that antioxidant vitamins do not provide any vascular protection. Moreover, several of these studies have demonstrated that antioxidant supplementation may be associated with an increased incidence of disease and mortality. One reason why these antioxidant vitamins may have failed to demonstrate benefit may have been due to inappropriate patient selection. In this review we provide supporting clinical evidence and a mechanistic basis for utilizing a genetic marker, the haptoglobin (Hp) genotype, in determining whether antioxidant vitamin therapy may or may not be beneficial for a given patient with diabetes.     

Cardiovascular risk factors and collateral artery formation

Arterial lumen narrowing and vascular occlusion is the actual cause of morbidity and mortality in atherosclerotic disease. Collateral artery formation (arteriogenesis) refers to an active remodelling of non-functional vascular anastomoses to functional collateral arteries, capable to bypass the site of obstruction and preserve the tissue that is jeopardized by ischaemia. Hemodynamic forces such as shear stress and wall stress play a pivotal role in collateral artery formation, accompanied by the expression of various cytokines and invasion of circulating leucocytes. Arteriogenesis hence represents an important compensatory mechanism for atherosclerotic vessel occlusion. As arteriogenesis mostly occurs when lumen narrowing by atherosclerotic plaques takes place, presence of cardiovascular risk factors (e.g. hypertension, hypercholesterolaemia and diabetes) is highly likely. Risk factors for atherosclerotic disease affect collateral artery growth directly and indirectly by altering hemodynamic forces or influencing cellular function and proliferation. Adequate collateralization varies significantly among atherosclerotic patients, some profit from the presence of extensive collateral networks, whereas others do not. Cardiovascular risk factors could increase the risk of adverse cardiovascular events in certain patients because of the reduced protection through an alternative vascular network. Likewise, drugs primarily thought to control cardiovascular risk factors might contribute or counteract collateral artery growth. This review summarizes current knowledge on the influence of cardiovascular risk factors and the effects of cardiovascular medication on the development of collateral vessels in experimental and clinical studies.     

运动与分岔血管剪切力及血液流变指标的变化

背景：运动后血液流变的异常是产生运动疲劳的原因之一,也是运动诱发心血管疾病的危险因素之一。目的：分析运动方式对血液流变指标和血管动力学的变化规律。方法：建立血管模型并采用有限元法分析一次性力竭运动和系统运动两种运动模式下分叉血管剪切力分布,检测30名健康大学生志愿者血液流变指标。在查阅文献的基础上,通过实验和理论分析运动方式对血液流变性的影响,及运动方式与血管剪切力之间的相关关系。结果与结论：一次性力竭运动能使机体血液流变性明显发生不良变化,而长期规律的系统运动后明显改变血液流变性均有向好方向发展的趋势。一次性力竭运动后,分叉血管剪切力在分岔处小于0.6 Pa;系统运动后,血管处剪切力为0.6-1 Pa。因此,一次性力竭运动后易诱发血管疾病;系统运动起到预防血管疾病的作用。