基质细胞血小板反应蛋白对可溶性鸟苷酸环化酶的调节：对血流的影响
Regulation of soluble guanylate cyclase by matricellular thrombospondins: implications for blood flow.
作者信息
Rogers Natasha M, Seeger Franziska, Garcin Elsa D, Roberts David D, Isenberg Jeffrey S
机构信息
Department of Medicine, Vascular Medicine Institute, University of Pittsburgh School of Medicine Pittsburgh, PA, USA.
Department of Chemistry and Biochemistry, University of Maryland Baltimore County Baltimore, MD, USA.
出版信息
Front Physiol. 2014 Apr 4;5:134. doi: 10.3389/fphys.2014.00134. eCollection 2014.
Nitric oxide (NO) maintains cardiovascular health by activating soluble guanylate cyclase (sGC) to increase cellular cGMP levels. Cardiovascular disease is characterized by decreased NO-sGC-cGMP signaling. Pharmacological activators and stimulators of sGC are being actively pursued as therapies for acute heart failure and pulmonary hypertension. Here we review molecular mechanisms that modulate sGC activity while emphasizing a novel biochemical pathway in which binding of the matricellular protein thrombospondin-1 (TSP1) to the cell surface receptor CD47 causes inhibition of sGC. We discuss the therapeutic implications of this pathway for blood flow, tissue perfusion, and cell survival under physiologic and disease conditions.
一氧化氮（NO）通过激活可溶性鸟苷酸环化酶（sGC）以提高细胞内环磷酸鸟苷（cGMP）水平来维持心血管健康。心血管疾病的特征是NO-sGC-cGMP信号传导减弱。sGC的药理激活剂和刺激剂正被积极探索作为治疗急性心力衰竭和肺动脉高压的方法。在此，我们综述调节sGC活性的分子机制，同时强调一种新的生化途径，即基质细胞蛋白血小板反应蛋白-1（TSP1）与细胞表面受体CD47结合会导致sGC受到抑制。我们讨论了该途径在生理和疾病条件下对血流、组织灌注和细胞存活的治疗意义。
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