Politécnico de Coimbra, ESTeSC, Ciências Biomédicas Laboratoriais, Rua 5 de Outubro, 3046-854 Coimbra, Portugal.
LABINSAÚDE - Laboratório de Investigação em Ciências Aplicadas à Saúde, Instituto Politécnico de Coimbra, ESTeSC, Rua 5 de Outubro, 3046-854 Coimbra, Portugal; Politécnico de Coimbra, ESTeSC, Fisiologia Clínica, Rua 5 de Outubro, 3046-854 Coimbra, Portugal.
Microvasc Res. 2022 Sep;143:104398. doi: 10.1016/j.mvr.2022.104398. Epub 2022 Jun 6.
Vascular diseases are the main cause of morbidity and mortality. The vascular extracellular matrix (ECM) is essential in mechanical support, also regulating the cellular behavior fundamental to vascular function and homeostasis. Vascular remodeling is an adaptive response to various physiological and pathological changes and is associated with aging and vascular diseases. The aim of this review is provide a general overview of the involvement of MMPs in the pathogenesis of vascular diseases, namely, arterial hypertension, atherosclerosis, aortic aneurysms and myocardial infarction. The change in the composition of the ECM by matrix metalloproteinases (MMPs) generates a pro-inflammatory microenvironment that modifies the phenotypes of endothelial cells and vascular smooth muscle cells. They play a central role in morphogenesis, tissue repair and remodeling in response to injury, e.g., after myocardial infarction, and in progression of diseases such as atherosclerosis. Alterations in specific MMPs could influence arterial remodeling and lead to various pathological disorders such as hypertension and aneurysm formation. MMPs are regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs), and the MMP/TIMP ratio generally determines the extent of ECM protein degradation and tissue remodeling. Studies are currently focused on improving the diagnostic and prognostic value of MMPs involved in the pathogenic process, increasing their therapeutic potential, and monitoring the disease. New selective MMP inhibitors may improve the specificity of these inhibitors, target specific MMPs in relevant pathological conditions and mitigate some of the side effects.
血管疾病是发病率和死亡率的主要原因。血管细胞外基质（ECM）在机械支撑中至关重要，还调节着血管功能和稳态的基本细胞行为。血管重构是对各种生理和病理变化的适应性反应，与衰老和血管疾病有关。本综述的目的是提供一个关于基质金属蛋白酶（MMPs）在血管疾病发病机制中的作用的概述，即动脉高血压、动脉粥样硬化、主动脉瘤和心肌梗死。基质金属蛋白酶（MMPs）改变 ECM 的组成，产生促炎微环境，改变内皮细胞和血管平滑肌细胞的表型。它们在形态发生、组织修复和对损伤的重塑中发挥核心作用，例如在心肌梗死后，以及在动脉粥样硬化等疾病的进展中。特定 MMPs 的改变可能会影响动脉重构，并导致各种病理紊乱，如高血压和动脉瘤形成。MMPs 受内源性金属蛋白酶组织抑制剂（TIMPs）的调节，MMP/TIMP 比值通常决定 ECM 蛋白降解和组织重塑的程度。目前的研究重点是提高参与发病过程的 MMPs 的诊断和预后价值，增加其治疗潜力，并监测疾病。新型选择性 MMP 抑制剂可能会提高这些抑制剂的特异性，针对相关病理条件下的特定 MMPs，并减轻一些副作用。
