LeBlanc Amanda J, Kelm Natia Q
Department of Physiology, Cardiovascular Innovation Institute, University of Louisville , Louisville, Kentucky.
Antioxid Redox Signal. 2017 Oct 20;27(12):785-801. doi: 10.1089/ars.2017.7292. Epub 2017 Sep 8.
Successful matching of cardiac metabolism to perfusion is accomplished primarily through vasodilation of the coronary resistance arterioles, but the mechanism that achieves this effect changes significantly as aging progresses and involves the contribution of reactive oxygen species (ROS). Recent Advances: A matricellular protein, thrombospondin-1 (Thbs-1), has been shown to be a prolific contributor to the production and modulation of ROS in large conductance vessels and in the peripheral circulation. Recently, the presence of physiologically relevant circulating Thbs-1 levels was proven to also disrupt vasodilation to nitric oxide (NO) in coronary arterioles from aged animals, negatively impacting coronary blood flow reserve.
This review seeks to reconcile how ROS can be successfully utilized as a substrate to mediate vasoreactivity in the coronary microcirculation as "normal" aging progresses, but will also examine how Thbs-1-induced ROS production leads to dysfunctional perfusion and eventual ischemia and why this is more of a concern in advancing age.
Current therapies that may effectively disrupt Thbs-1 and its receptor CD47 in the vascular wall and areas for future exploration will be discussed. Antioxid. Redox Signal. 27, 785-801.
心脏代谢与灌注的成功匹配主要通过冠状动脉阻力小动脉的血管舒张来实现，但随着衰老的进展，实现这种效应的机制会发生显著变化，且涉及活性氧（ROS）的作用。最新进展：一种基质细胞蛋白，血小板反应蛋白-1（Thbs-1），已被证明在大电导血管和外周循环中对ROS的产生和调节有很大作用。最近，已证实生理相关的循环Thbs-1水平的存在也会破坏老年动物冠状动脉小动脉对一氧化氮（NO）的血管舒张作用，对冠状动脉血流储备产生负面影响。
本综述旨在探讨随着“正常”衰老的进展，ROS如何能够成功地作为一种底物来介导冠状动脉微循环中的血管反应性，同时也将研究Thbs-1诱导的ROS产生如何导致灌注功能障碍以及最终的缺血，以及为什么这在老年时更值得关注。
将讨论目前可能有效破坏血管壁中Thbs-1及其受体CD47的疗法以及未来的探索领域。《抗氧化与氧化还原信号》27卷，第785 - 801页。
