程序性细胞死亡与血管钙化关系的研究进展

血管钙化是多种疾病的并发症之一,并参与疾病的发生发展。而血管平滑肌细胞死亡是钙化过程中的必然伴随现象。已有研究证明血管平滑肌细胞的凋亡明确参加血管钙化的发生,而对于另一种程序性细胞死亡方式——自噬是否参与血管平滑肌细胞钙化研究近年来也有报道。本文就当今凋亡和自噬两种常见细胞程序性死亡参与血管平滑肌钙化的作用及可能机制以及影响因素的研究进展作一综述。     

炎症相关microRNA与血管钙化

血管钙化指钙磷在血管壁的异位沉积,常见于糖尿病、动脉粥样硬化、慢性肾脏病等慢性炎症疾病,与心血管疾病的发病率和病死率密切相关。血管钙化作为一种慢性炎症状态,炎症因子在其中具有重要调控作用。作为一种非编码小RNA的microRNA,许多研究证实其可以通过调控血管平滑肌细胞的表型转换、钙磷稳态、局部及系统炎症因子表达等来引起血管钙化的发生发展。目前发现的microRNA种类较多,本文对炎症与血管钙化的关系以及炎症相关microRNA如何通过调控炎症因子表达影响血管钙化过程进行综述,希望能为进一步探究血管钙化机制及临床预防、治疗血管钙化提供新思路。     

Notch1信号通路与血管钙化

Notch1信号通路是一个高度保守的信号转导通路,参与胚胎期血管的形成及发育以及出生后对损伤血管的修复等。血管钙化是羟基磷灰石在血管壁细胞的沉积,受多种调节因子、信号通路影响,是一个可主动调节、类似于骨形成的生物学过程。近年来研究表明Notch1信号通路与血管钙化存在密切关系。本文就Notch1信号通路的组成、效应传递及生理功能,血管钙化的发生机制及调节,以及Notch1信号通路与血管钙化的关系作一综述。     

血管钙化的表观遗传调控

血管钙化是慢性肾病、糖尿病、高血压和动脉粥样硬化等疾病共同存在的血管病变,其是上述疾病患者心血管事件显著上升的重要危险因素。目前尚无有效药物可以预防或者逆转血管钙化。既往研究表明,血管钙化是一个主动的、可调控的、细胞介导的病理过程,高度类似于骨发生和骨代谢。血管平滑肌细胞向成骨样细胞转分化是血管钙化发生的关键机制。目前的研究表明,多种表观遗传调控途径参与血管钙化的病理进程。本文主要从DNA甲基化、组蛋白修饰和非编码RNA这三个层面综述血管钙化的表观遗传调控机制。靶向表观遗传调控因子有望为防治血管钙化提供新的策略。     

低氧诱导因子1α与血管钙化关系的研究进展

低氧诱导因子1α(HIF-1α)是细胞在低氧环境下产生的高度特异性核转录因子,在骨形成及骨再生修复中发挥重要作用。血管钙化是一个与骨形成类似、主动调节的复杂生物学过程,是心血管死亡率增加的主要危险因素,但其发生机制尚未完全阐明。新近的研究表明HIF-1α可通过调节血管平滑肌细胞(VSMC)成骨样分化、糖代谢途径、炎症、Notch信号通路等机制参与血管钙化。本文就HIF-1α与血管钙化的关系作一综述。     

钾离子与血管钙化调节研究进展

<正>血管钙化(vascular calcification)是血管壁上钙盐的过量沉积,是血管壁上的异位骨形成。血管钙化是动脉粥样硬化、高血压、糖尿病、肾病等多种疾病的病理基础,是脑卒中、心脏病等多种心血管病的主要危险因素。因此,血管钙化研究一直是心脑血管病与肾病研究的热点。钙化的确切机制,迄今不明。近10年来,对血管钙化致病机制的研究结果显示,血管钙化与骨形成过程类似,是一个主动的可调控过程。多种因子,如蛋白质、维生素和无机小分子都参与了钙化过程的调节,但直接研究钾离子与血管钙化的关系,鲜见报道。一些关于血管钙化致病机制的研究结果间接表明,钾离子可能参与了血管钙化的调节。因此,我们对相关文献进     

外泌体介导血管平滑肌细胞钙化的研究进展

外泌体(exosome)是由细胞内分泌到细胞外的纳米级别的基质囊泡,具有磷脂双分子层结构,内含多种细胞特异的脂质、核酸及蛋白质等,主要参与细胞间通讯、免疫调节以及细胞信号通路调节等过程。近年来,研究发现外泌体在血管平滑肌细胞钙化的发生、发展过程中发挥着重要作用。了解外泌体调节血管平滑肌细胞钙化的机制,对未来临床预防血管平滑肌细胞钙化及降低心血管疾病发生风险有重要作用。     

关注血管钙化和骨质疏松共同发病机制

老年血管钙化、动脉粥样硬化病人,慢性肾功能衰竭进行肾透析以及接受维生素D和华法林治疗的患者常并存骨质疏松症.近年流行病学、血管和细胞生物学、影像学及治疗学的发展证实血管钙化和骨质疏松具有共同的发病机制.除传统引起血管钙化和骨质疏松的因素外,基质Gla蛋白、骨桥蛋白、Klotho蛋白、胎球蛋白A以及RANKL/RANK/OPG系统均参与了血管钙化和骨质疏松的发生发展.     

铁稳态在血管钙化发病机制中的作用

心血管疾病(CVD)在全球范围具有高发病率、高致残率和高致死率的特点,而血管钙化(VC)是造成CVD风险事件终末结局的主要共同病理改变,表明血管钙化是CVD的潜在防治靶点,但鉴于血管钙化的复杂发病机制,目前没有应对血管钙化的有效手段。铁是人体必需的微量元素,研究发现铁含量超载或缺乏导致的铁稳态(IH)异常分别在不同类型的CVD和疾病不同阶段参与血管钙化的发生发展。因此,阐明血管钙化时的铁稳态异常机制,有助于为血管钙化的基础研究和临床防治指出新方向。     

骨保护素与糖尿病及其血管并发症

骨保护素（OPG）是肿瘤坏死因子受体超家族成员,是骨代谢的一个重要调节因子。近来研究发现,OPG亦是重要的血管调节因子,能够保护血管内皮细胞,抑制血管钙化。糖尿病微血管及大血管并发症患者血清OPG水平明显升高,血清OPG水平与糖尿病并发症密切相关,OPG在糖尿病并发症的发生、发展中可能起重要的调节作用。确切的机制尚不清楚,可能是一种自我代偿机制,以对抗促动脉硬化、血管钙化及血管损伤的其他因子。     

Large vessel calcification in Takayasu arteritis

We report the novel case of a young woman with Takayasu arteritis, with extensive large vessel disease. The case demonstrates that while mechanisms of vascular calcification are poorly understood, inflammation per se might be sufficient to mediate increased mineral stress leading to vessel calcification, even in the absence of renal impairment.     

Atherosclerosis and vascular calcification in hemodialysis patients

Cardiovascular disease is the largest cause of mortality in hemodialysis patients. Cardiovascular mortality is fivefold to twentyfold higher in hemodialysis patients than in the general population. Atherosclerosis and vascular calcification are the characteristic complications in hemodialysis patients. Hemodialysis patients have traditional risk factors such as abnormal lipid metabolism and uremia-related risk factors such as oxidative stress and hyperphosphatemia. Oxidative stress takes place by increased production of oxidants by leukocytes and antioxidant loss of vitamin C and E. Oxidatively modified LDL exist in the circulation by excess of oxidative stress in hemodialysis patients. Oxidative stress is a major contributor to accelerated development atherosclerosis. Oxidative stress and hyperphosphatemia also influence vascular calcification. The pattern of vascular calcification in hemodialysis patient is characterized by mineral deposition in the tunica media. It is reported that the obvious calcification in aorta and artery of the MGP knockout mouse is recognized. It is indicated that MGP has the inhibitory effect of the calcification of vessel wall. Vitamin E protects atherosclerosis and vascular calcification in hemodialysis patients. It is also important to control hyperphosphatemia for vascular calcification.     

Significance of vascular calcification in diabetic patients with increased risks of cardiovascular disease and stroke

Patients with diabetes have greatly elevated risks of atherosclerotic diseases such as coronary artery disease (CAD) and stroke. Vascular calcification in advanced atherosclerosis is a common feature in diabetic patients. In vitro and in vivo studies suggest that apoptosis and chondro/osteogenic differentiation of vascular wall cells such as smooth muscle cells may play important roles in the progression of vascular calcification. Diabetes may promote vascular calcification through the action of various factors including hyperglycemia, oxidative stress, tumor necrosis factor-alpha, and advanced glycation end products. Detection of coronary calcium by electron-beam computed tomography (EBCT) revealed clinical significance of vascular calcification and this technique may be a useful method to identify diabetic patients with increased risks of cardiovascular disease and stroke.     

关注血管钙化的起源、演进与转归研究

血管钙化是动脉壁间叶细胞尤其是平滑肌细胞在各种病理因素作用下转分化为成骨成软骨细胞表型,介导钙盐异常沉积在血管壁的过程,包括内膜钙化、中膜钙化及瓣膜钙化等多种病理类型。随着我国老龄化趋势的不断加剧,尤其是糖尿病、动脉粥样硬化及慢性肾脏病等的患病率持续走高,由其衍生的血管钙化正在逐渐演变为影响我国人民健康的一个关键疾病谱。为此,本文从血管钙化的起源、演进及转归,尤其是转归过程中的骨与血管、主动与被动、内膜钙化与中膜钙化、微钙化与大钙化以及自噬、内质网应激和非编码RNA等争议和热点问题入手,进行了系统阐述,希冀通过本文和专栏内多位专家以及一直奋战在钙化领域内广大同道的共同努力,一起推动血管钙化基础与临床研究的前行。     

血管平滑肌细胞表型的成骨转换与血管钙化

血管钙化是血管壁中钙盐沉积的过程,导致血管硬化和失去弹性。它通常发生在中老年人,尤其是患有动脉粥样硬化、高血压、糖尿病和慢性肾脏疾病等疾病患者。血管钙化是一个主动的过程,其中平滑肌细胞的成骨转换是重要事件之一。这些细胞在钙化过程中释放钙离子,导致钙盐的沉积,形成钙化斑块。血管钙化受多种因素调节,包括高磷、高钙水平及氧化应激、机械应力等。此外,中医药研究在减轻血管钙化方面显示出潜力,例如灵芝孢子粉和其衍生物,三七、黄芩素、根皮素、雷公藤甲素等。这些研究为进一步理解和干预血管钙化提供了重要的证据,并揭示了一些潜在的抑制因子,可以作为未来治疗血管钙化的研究方向。     

Arterial ageing: from endothelial dysfunction to vascular calcification

Complex structural and functional changes occur in the arterial system with advancing age. The aged artery is characterized by changes in microRNA expression patterns, autophagy, smooth muscle cell migration and proliferation, and arterial calcification with progressively increased mechanical vessel rigidity and stiffness. With age the vascular smooth muscle cells modify their phenotype from contractile to ‘synthetic’ determining the development of intimal thickening as early as the second decade of life as an adaptive response to forces acting on the arterial wall. The increased permeability observed in intimal thickening could represent the substrate on which low‐level atherosclerotic stimuli can promote the development of advanced atherosclerotic lesions. In elderly patients the atherosclerotic plaques tend to be larger with increased vascular stenosis. In these plaques there is a progressive accumulation of both lipids and collagen and a decrease of inflammation. Similarly the plaques from elderly patients show more calcification as compared with those from younger patients. The coronary artery calcium score is a well‐established marker of adverse cardiovascular outcomes. The presence of diffuse calcification in a severely stenotic segment probably induces changes in mechanical properties and shear stress of the arterial wall favouring the rupture of a vulnerable lesion in a less stenotic adjacent segment. Oxidative stress and inflammation appear to be the two primary pathological mechanisms of ageing‐related endothelial dysfunction even in the absence of clinical disease. Arterial ageing is no longer considered an inexorable process. Only a better understanding of the link between ageing and vascular dysfunction can lead to significant advances in both preventative and therapeutic treatments with the aim that in the future vascular ageing may be halted or even reversed.     

Vascular failure: A new clinical entity for vascular disease

Atherosclerosis is characterized by the response of the vessel wall to chronic multifactorial injury leading to the formation of atheromatous or fibrous plaques. Endothelial dysfunction represents an initial stage of atherosclerosis. In addition to endothelial dysfunction, smooth muscle dysfunction, metabolic abnormalities of the vessel wall including inflammation, oxidative stress and alterations of neurohormonal balance occur in various stages of atherosclerosis. We now propose a new clinical entity 'vascular failure', defined as the integration of all of these vascular abnormalities. Vascular failure is not an anatomical disease, but rather a comprehensive syndrome of abnormal vascular function. Vascular failure extends from risk factors to established atherosclerotic disease with arterial stenosis, and further to calcification of the vessel wall or serious vascular events that may be caused by plaque rupture and thromboembolic occlusion. We propose aggressive intervention to modify various risk factors, applying to this integrated new entity, vascular failure.     

Vascular calcification in rheumatoid arthritis: Prevalence, pathophysiological aspects and potential targets

Individuals with rheumatoid arthritis (RA) are at increased risk for morbidity and mortality from cardiovascular disease. Excess cardiovascular mortality in RA patients cannot be fully explained by conventional cardiovascular risk factors. The purpose of this review is to discuss recent progress concerning the prevalence and pathophysiological aspects of vascular calcification in RA. RA patients have early-onset diffuse calcification involving multiple vascular beds compared to age and sex-matched controls. Pathogenesis of vascular calcification in RA patients is not fully understood, but specific mediators such as proinflammatory cytokines and not global inflammation could be involved. The possible link between osteoporosis and vascular calcification in RA will not be discussed. Finally, potential targets to reduce vascular calcification in RA will be discussed.     

Theodore Cooper Lecture: Tissue angiotensin and pathobiology of vascular disease: a unifying hypothesis

There is increasing evidence that direct pathobiological events in the vessel wall play an important role in vascular disease. An important mechanism involves the perturbation of the homeostatic balance between NO and reactive oxygen species. Increased reactive oxygen species can inactivate NO and produce peroxynitrite. Angiotensin II is a potent mediator of oxidative stress and stimulates the release of cytokines and the expression of leukocyte adhesion molecules that mediate vessel wall inflammation. Inflammatory cells release enzymes (including ACE) that generate angiotensin II. Thus, a local positive-feedback mechanism could be established in the vessel wall for oxidative stress, inflammation, and endothelial dysfunction. Angiotensin II also acts as a direct growth factor for vascular smooth muscle cells and can stimulate the local production of metalloproteinases and plasminogen activator inhibitor. Taken together, angiotensin II can promote vasoconstriction, inflammation, thrombosis, and vascular remodeling. In this article, we propose a model that unifies the interrelationship among cardiovascular risk factors, angiotensin II, and the pathobiological mechanisms contributing to cardiovascular disease. This model may also explain the beneficial effects of ACE inhibitors on cardiovascular events beyond blood pressure reduction.     

糖尿病与血管钙化

血管钙化是糖尿病患者的一个常见并发症,包括血管内膜钙化和中膜钙化,呈进展性,是糖尿病患者心血管疾病及全因死亡的预测因子。糖尿病血管钙化是多种促进和抑制钙化的因素参与的细胞介导的主动调节过程,高血糖、胰岛素抵抗、肾脏疾病、炎症、骨相关蛋白表达异常等多种因素与其相关。对于糖尿病血管钙化,目前尚无有效的治疗手段,及时评价和控制血管钙化的危险因素,进行合理的预防性治疗非常重要。