动脉粥样硬化斑块内血管生成的研究进展及治疗策略

动脉粥样硬化斑块破裂或糜烂引发的急性心血管事件是患者死亡的主要原因。斑块内血管生成是促进斑块生长并造成斑块不稳定的重要因素之一。新生的血管发育不成熟,存在结构和功能的异常,导致反复发生斑块内出血。现从斑块内血管生成促进动脉粥样硬化发展的机制、检测血管生成的影像学方法以及抗血管生成的治疗策略等方面进行综述。     

动脉粥样硬化斑块内血管新生的研究进展

斑块内血管新生在动脉粥样硬化的发生发展中可能是一个核心事件并起着关键性作用 ,进一步研究新生血管的发生机制及其病理生理意义并寻求较佳的防治方法 ,可以为认识动脉粥样硬化的发病机制和防治动脉粥样硬化提供一个新的视点。     

心外膜脂肪因子促进血管新生的分子机制

心外膜脂肪组织是沉积在心脏尤其是冠状动脉周围的脂肪组织，可以表达多种脂肪因子参与动脉粥样硬化的发生与发展，最近这些脂肪因子已经被证实还可以引起冠状动脉粥样硬化斑块内的血管新生。这些新生血管在斑块内可能具有双重效应：一方面，新生血管具有很强的通透性，可以改善斑块局部缺氧状况；另一方面，新生血管可能促进斑块进展并导致其不稳定性增加。因此，通过研究脂肪因子致血管新生作用的机制，抑制斑块内的血管新生增强其稳定性可能成为未来治疗冠心病新的靶点。     

颈动脉粥样硬化斑块内新生血管的研究现状及进展

颈动脉粥样硬化斑块破裂是导致脑卒中的重要原因之一,大量研究证实颈动脉斑块内新生血管是导致斑块内出血、斑块破裂的重要因素。炎症因子及各类细胞通过斑块内新生血管进入斑块,导致斑块稳定性破坏,但影响斑块内新生血管形成的重要相关因子和主要机制目前尚未完全明确,因此识别斑块内新生血管、探索斑块内新生血管形成的相关因子及机制是研究斑块内新生血管致斑块不稳定性的关键。抑制斑块内新生血管生成,可能成为防治颈动脉斑块破裂、降低脑栓塞事件发生的新策略。本综述旨在探讨颈动脉斑块内新生血管形成的相关因子、机制以及检测成像的最新研究进展,为动脉粥样硬化的诊疗提供支持。     

血管新生对动脉粥样硬化斑块稳定性影响的研究进展

斑块内血管新生由低氧和炎症等因素诱导形成,在动脉粥样硬化斑块的发生发展中发挥了重要作用。一方面通过加剧炎症反应和诱发斑块内出血,影响斑块的稳定性,从而诱发死亡率极高的急性冠状动脉综合征;另一方面可缓解斑块内低氧状态,减少细胞坏死,为斑块内有害物质的移出提供通道。抗血管生成治疗虽已投入临床应用,但在动脉粥样硬化方面进展甚小。本文就斑块内新生血管形成发生机制、血管新生对动脉粥样硬化斑块稳定性的影响及其相关临床应用进展作一综述。     

动脉粥样硬化斑块内血管新生的研究进展

动脉粥样硬化是诱导心脑血管相关疾病发生的主要原因,在动脉粥样硬化的影响因素中,血管新生是导致斑块内破裂并引发各种并发症的主要原因之一。缺氧、炎症、生长因子相关因素可引发斑块内血管新生,导致动脉粥样硬化的发生。本文对影响血管新生的相关因素及其作用机制作一综述,为动脉粥样硬化的防治提供新的思路和干预靶点。     

内皮祖细胞在动脉粥样硬化进程中的作用

内皮祖细胞因参与再内皮化和血管新生,在动脉粥样硬化病变发生发展中可能起着举足轻重的作用,包括参与内皮损伤后修复与内膜增生,影响斑块发展与稳定以及对动脉粥样硬化性疾病严重程度的预测。动脉粥样硬化病变过程中若干危险因素影响了内皮祖细胞的数量和功能,从而削弱内皮祖细胞可能的血管保护作用并影响动脉粥样硬化进程,因而提出内皮祖细胞潜在的治疗作用。本文从再内皮化、斑块发展和血管新生、动脉粥样硬化的若干危险因素及内皮祖细胞的预测价值和治疗作用等方面对内皮祖细胞在动脉粥样硬化进程中的作用作一综述。     

超声造影评价颈动脉斑块内新生血管的研究进展

动脉粥样硬化斑块与心脑血管事件的发生密切相关,早期评估动脉粥样硬化斑块的稳定性对于预防心脑血管事件发生及制定治疗方案十分重要。大量研究证实斑块内新生血管与斑块的稳定性有关,超声造影可显示和评估颈动脉斑块内新生血管,是近年来斑块稳定性研究的热点技术之一。     

动脉粥样硬化斑块内间质微环境与新生血管生成关系的最新研究进展

近几年,对动脉粥样硬化斑块内间质微环境的研究和认识越来越深,尤其在与新生血管的生成关系方面突破最大。随着研究的深入,人们对间质微环境的的分类、来源以及与血管生成有了更多的认识。现综述动脉粥样硬化斑块内间质微环境与新生血管生成关系的最新研究进展。     

单个核细胞分化的命运与动脉粥样硬化

血管新生是指在原来存在的血管结构上长出新血管的生物学过程。急性冠状动脉综合征(ACS)主要为斑块破裂和血栓形成所引起,斑块内血管新生是斑块破裂的一个重要危险因素。而力学微环境与血管新生及微血管破裂关系密切,现阐述力学环境与斑块内血管新生的关系。①血管新生的力学微环境。动脉粥样硬化斑块因血管平滑肌细胞大量增殖和胶原大量沉积,引起微血管内腔压力增加,包括外膜的血管网所受压力上升,血管网血流压力梯度增强,局部....     

Novel techniques and targets in cardiovascular microRNA research

MicroRNAs (miRNAs) are highly conserved, tiny (～22 nucleotides) non-coding RNAs that have emerged as potent regulators of mRNA translation. miRNAs exhibit fine-tuning of the control of proteins involved in cell signalling (AE) pathways and in vital cellular and developmental processes. miRNAs are expressed in cardiovascular tissues, and multiple functional aspects of miRNAs underscore their key role in cardiovascular (patho)physiology. The development and increasing use of novel molecular biology tools have contributed to the recent success in miRNA research. In the present review, we discuss current updates on important and novel miRNA techniques, including: (i) miRNA screening tools; (ii) bioanalytical target prediction tools; (iii) target validation tools; and (iv) manipulative miRNA expression tools. We also present an update about recently identified miRNA targets that play a key role in cardiovascular development and disorders.     

microRNAs在心血管生物学及心血管疾病中的研究进展

心血管疾病是导致人类死亡的主要原因之一,心血管疾病所引起人类死亡约占全球死亡总数的30%。microRNAs(miRNAs)是一类通过调节靶mRNA转录或转录后翻译诱导靶基因表达沉默而发挥广泛生物学作用的非编码RNA。近年来,大量研究表明:miRNAs在哺乳动物心血管系统中广泛表达并在多种心血管疾病的病理发生过程中发挥着关键的调节作用,包括心脏重构、缺血性心脏疾病以及心律不齐等。miRNAs在心血管疾病中如此广泛的作用为阐明心血管疾病的发病机制提供了新的视角并为心血管疾病的诊断与治疗提供了新的靶点。     

Role of microRNAs in stem/progenitor cells and cardiovascular repair

MicroRNAs (miRNAs), small non-coding RNAs, play a critical role in differentiation and self-renewal of pluripotent stem cells, as well as in differentiation of cardiovascular lineage cells. Several miRNAs have been demonstrated to repress stemness factors such as Oct4, Nanog, Sox2 and Klf4 in embryonic stem cells, thereby promoting embryonic stem cell differentiation. Furthermore, targeting of different miRNAs promotes reprogramming towards induced pluripotent stem cells. MicroRNAs are critical for vascular smooth muscle cell differentiation and phenotype regulation, and miR-143 and miR-145 play a particularly important role in this respect. Notably, these miRNAs are down-regulated in several cardiovascular disease states, such as in atherosclerotic lesions and vascular neointima formation. MicroRNAs are critical regulators of endothelial cell differentiation and ischaemia-induced neovascularization. miR-126 is important for vascular integrity, endothelial cell proliferation and neovascularization. miR-1 and miR-133 are highly expressed in cardiomyocytes and their precursors and regulate cardiomyogenesis. In addition, miR-499 promotes differentiation of cardiomyocyte progenitor cells. Notably, miRNA expression is altered in cardiovascular disease states, and recent studies suggest that dysregulated miRNAs may limit cardiovascular repair responses. Dysregulation of miRNAs may lead to an altered function and differentiation of cardiovascular progenitor cells, which is also likely to represent a limitation of autologous cell-based treatment approaches in these patients. These findings suggest that targeting of specific miRNAs may represent an interesting novel opportunity to impact on endogenous cardiovascular repair responses, including effects on stem/progenitor cell differentiation and functions. This approach may also serve to optimize cell-based treatment approaches in patients with cardiovascular disease.     

A new level of complexity: the role of microRNAs in cardiovascular development

The discovery of the regulatory role of noncoding RNAs, and micro (mi)RNAs in particular, has added a new layer of complexity to our understanding of cardiovascular development. miRNAs regulate and modulate various steps of cardiovascular morphogenesis, cell proliferation, differentiation, and phenotype modulation. miRNAs simultaneously regulate multiple targets, and many miRNAs can bind to the same target, allowing for a complex pattern of regulation of gene expression. miRNA families are continuously added during evolution paralleling the increased complexity of the cardiovascular system in vertebrates compared with invertebrates. Several lines of evidence suggest that the appearance of miRNAs is at least in part responsible for the formation of complex organ systems and stable regulatory mechanisms in vertebrates. We review the current understanding of miRNAs during cardiovascular development. Further progress in this area will help to decipher quantitative changes in gene expression that provide robustness to cellular phenotypes and regulatory options to diseases processes. miRNAs might also provide clues to better understand congenital heart defects, which are the most common birth defects in human newborns.     

MicroRNA-based therapeutic approaches in the cardiovascular system

MicroRNAs (miRNAs) are endogenous small ribonucleotides that participate in the orchestration of the genome by regulating target messenger RNA translation. MiRNAs control physiological processes and misexpression of miRNAs is pathogenically involved in many diseases including cardiovascular diseases. Normalization of miRNA expression and thus downstream target networks may have enormous therapeutic chances but also risks. We here highlight and discuss recent advances in the development and use of miRNA therapeutics to target miRNAs in vivo that may translate into novel therapeutic strategies for cardiovascular diseases in the future.     

miRNA在心血管疾病中的研究进展

MicroRNAs（miRNAs）是一类长度为21~25个核糖核苷酸的非编码内源性小单链RNAs分子,在转录后水平调控蛋白质的表达,几乎参与所有生命体的生理和病理过程。最近研究显示miRNAs在心血管系统发生及病理生理方面发挥至关重要作用。循环miRNAs概念的引入,使得对其研究变得更加方便,可能作为新的心血管疾病生物标志物。本文就miRNA在心血管方面的研究进展加以综述。     

循环microRNAs在心血管疾病中的研究及应用

MicroRNAs（miRNAs）在心脏的生长、发育及心血管疾病的发生、发展等过程中起着十分重要的作用。近年来,在人血浆/血清中检测到稳定性良好的miRNA称之为循环miRNAs。在正常人和各种疾病患者体内循环miRNAs的表达谱存在明显的差异,因此循环miRNAs很可能成为多种疾病的新型诊断标志物。现对循环miRNAs的发现、产生机制、检测方法以及其在心血管疾病领域研究进展及临床应用前景进行综述。