Diviani Dario, Reggi Erica, Arambasic Miroslav, Caso Stefania, Maric Darko
Département de Pharmacologie et de Toxicologie, Faculté de Biologie et de Médecine, Lausanne 1005, Switzerland.
Département de Pharmacologie et de Toxicologie, Faculté de Biologie et de Médecine, Lausanne 1005, Switzerland.
Biochim Biophys Acta. 2016 Jul;1863(7 Pt B):1926-36. doi: 10.1016/j.bbamcr.2015.11.024. Epub 2015 Nov 28.
Heart and blood vessels ensure adequate perfusion of peripheral organs with blood and nutrients. Alteration of the homeostatic functions of the cardiovascular system can cause hypertension, atherosclerosis, and coronary artery disease leading to heart injury and failure. A-kinase anchoring proteins (AKAPs) constitute a family of scaffolding proteins that are crucially involved in modulating the function of the cardiovascular system both under physiological and pathological conditions. AKAPs assemble multifunctional signaling complexes that ensure correct targeting of the cAMP-dependent protein kinase (PKA) as well as other signaling enzymes to precise subcellular compartments. This allows local regulation of specific effector proteins that control the function of vascular and cardiac cells. This review will focus on recent advances illustrating the role of AKAPs in cardiovascular pathophysiology. The accent will be mainly placed on the molecular events linked to the control of vascular integrity and blood pressure as well as on the cardiac remodeling process associated with heart failure. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.
心脏和血管确保外周器官获得充足的血液和营养物质灌注。心血管系统稳态功能的改变可导致高血压、动脉粥样硬化和冠状动脉疾病,进而引发心脏损伤和衰竭。A激酶锚定蛋白(AKAPs)构成了一类支架蛋白家族,在生理和病理条件下都对调节心血管系统的功能起着至关重要的作用。AKAPs组装多功能信号复合物,确保环磷酸腺苷依赖性蛋白激酶(PKA)以及其他信号酶准确靶向特定的亚细胞区室。这使得能够对控制血管和心脏细胞功能的特定效应蛋白进行局部调节。本综述将聚焦于阐述AKAPs在心血管病理生理学中作用的最新进展。重点将主要放在与血管完整性和血压控制相关的分子事件,以及与心力衰竭相关的心脏重塑过程上。本文是由Marcus Schaub和Hughes Abriel编辑的名为《心肌细胞生物学:心脏发育与环境信号的整合》特刊的一部分。