First Department of Cardiology, 'Hippokration' Hospital, Medical School, University of Athens, Athens, Greece.
Acta Cardiol. 2021 Jun;76(4):335-348. doi: 10.1080/00015385.2020.1746053. Epub 2020 Jun 30.
Aortic valve stenosis is a degenerative disease affecting increasing number of individuals and characterised by thickening, calcification and fibrosis of the valve resulting in restricted valve motion. Degeneration of the aortic valve is no longer considered a passive deposition of calcium, but an active process that involves certain mechanisms, that is endothelial dysfunction, inflammation, increased oxidative stress, calcification, bone formation, lipid deposition, extracellular matrix (ECM) remodelling and neoangiogenesis. Accumulating evidence indicates an important role for neoangiogenesis (i.e. formation of new vessels) in the pathogenesis of aortic valve stenosis. The normal aortic valve is generally an avascular tissue supplied with oxygen and nutrients diffusion from the circulating blood. In contrast, presence of intrinsic micro-vasculature has been demonstrated in stenotic and calcified valves. Importantly, presence and density of neovessels have been associated with inflammation, calcification and bone formation. It remains unclear whether neoangiogenesis is a compensatory mechanism aiming to counteract hypoxia and increased metabolic demands of the thickened tissue or represents an active contributor to disease progression. Data extracted mainly from animal studies are supportive of a direct detrimental effect of neoangiogenesis, however, robust evidence from human studies is lacking. Thus, there is inadequate knowledge to assess whether neoangiogenesis could serve as a future therapeutic target for a disease that no effective medical therapy exists. In this review, we present basic aspects of anatomy and structure of the normal and stenotic aortic valve and we focus on the role of valve vasculature in the natural course of valve calcification and stenosis.
主动脉瓣狭窄是一种退行性疾病，影响的人数不断增加，其特征是瓣膜增厚、钙化和纤维化，导致瓣膜运动受限。主动脉瓣的退化不再被认为是钙的被动沉积，而是一种涉及特定机制的主动过程，即内皮功能障碍、炎症、氧化应激增加、钙化、骨形成、脂质沉积、细胞外基质 (ECM) 重塑和新生血管形成。越来越多的证据表明，新生血管形成（即新血管的形成）在主动脉瓣狭窄的发病机制中起重要作用。正常的主动脉瓣通常是一种无血管组织，通过循环血液中的扩散获得氧气和营养物质。相比之下，在狭窄和钙化的瓣膜中已经证明存在固有微血管。重要的是，新血管的存在和密度与炎症、钙化和骨形成有关。新生血管形成是一种旨在对抗增厚组织缺氧和代谢需求增加的代偿机制，还是疾病进展的主动因素，目前尚不清楚。主要从动物研究中提取的数据支持新生血管形成的直接有害作用，但是缺乏来自人体研究的有力证据。因此，对于一种尚无有效治疗方法的疾病，评估新生血管形成是否可以作为未来的治疗靶点的知识还不够充分。在这篇综述中，我们介绍了正常和狭窄主动脉瓣的解剖和结构的基本方面，并重点介绍了瓣膜血管在瓣膜钙化和狭窄自然病程中的作用。
