Fierro-Macías Alfonso Eduardo, Floriano-Sánchez Esaú, Mena-Burciaga Victoria Michelle, Gutiérrez-Leonard Hugo, Lara-Padilla Eleazar, Abarca-Rojano Edgar, Fierro-Almanzán Alfonso Edmundo
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, DF, México.
Laboratorio Multidisciplinario de Investigación, Escuela Militar de Graduados de Sanidad, Secretaría de la Defensa Nacional (SEDENA), México, DF, México.
Arch Cardiol Mex. 2016 Apr-Jun;86(2):148-56. doi: 10.1016/j.acmx.2015.12.006. Epub 2016 Feb 18.
Atherosclerosis is a condition that involves multiple pathophysiological mechanisms and whose knowledge has not been fully elucidated. Often, scientific advances on the atherogenic pathophysiology generate that molecules not previously considered in the scene of this disease, were attributed actions on the onset or progression of it. A representative example is the study of a new mechanism involved in the atherogenic process, consisting of the association between the insulin-like growth factor (IGF) system and pregnancy-associated plasma protein-A (PAPP-A). Insulin-like growth factor system is a family of peptides that include 3 peptide hormones, 4 transmembrane receptors and 6 binding proteins. Insulin-like growth factor-1 (IGF-1) is the main ligand of the IGF system involved in coronary atherosclerosis. IGF-1 exerts its effects via activation of the IGF-1R receptor on vascular smooth muscle cells or macrophages. In vascular smooth muscle cells promotes migration and prevents apoptosis which increases plaque stability while in macrophages reduces reverse cholesterol transport leading to the formation of foam cells. Regulation of IGF-1 endothelial bioavailability is carried out by IGFBP proteases, mainly by PAPP-A. In this review, we address the mechanisms between IGF system and PAPP-A in atherosclerosis with emphasis on molecular effects on vascular smooth muscle cells and macrophages.
动脉粥样硬化是一种涉及多种病理生理机制的疾病,其相关知识尚未完全阐明。通常,动脉粥样硬化病理生理学的科学进展使得一些此前未在该疾病领域被考虑的分子,被认为对其发病或进展有作用。一个典型的例子是对动脉粥样硬化过程中一种新机制的研究,该机制由胰岛素样生长因子(IGF)系统与妊娠相关血浆蛋白-A(PAPP-A)之间的关联组成。胰岛素样生长因子系统是一个肽家族,包括3种肽激素、4种跨膜受体和6种结合蛋白。胰岛素样生长因子-1(IGF-1)是IGF系统中参与冠状动脉粥样硬化的主要配体。IGF-1通过激活血管平滑肌细胞或巨噬细胞上的IGF-1R受体发挥作用。在血管平滑肌细胞中,它促进迁移并防止细胞凋亡,从而增加斑块稳定性;而在巨噬细胞中,它减少胆固醇逆向转运,导致泡沫细胞形成。IGF-1在内皮细胞中的生物利用度由IGFBP蛋白酶调节,主要是由PAPP-A调节。在本综述中,我们阐述了IGF系统与PAPP-A在动脉粥样硬化中的机制,重点是对血管平滑肌细胞和巨噬细胞的分子效应。