Guazzi Marco, Vicenzi Marco, Samaja Michele
Unità Cardiopolmonare, Ospedale San Paolo, Università degli Studi, Milano.
G Ital Cardiol (Rome). 2009 Nov-Dec;10(11-12):725-37.
Phosphodiesterases are a class of proteins that primarily modulate intracellular levels of cyclic nucleotides such as cGMP and cAMP. Phosphodiesterase-5 (PDE5) is mainly involved in the smooth muscle cell cGMP inactivation. Chemical inhibition of PDE5 has recently become a valid therapeutic option of nitric oxide pathway potentiation via cell cGMP availability. More specifically, PDE5 inhibition appears successful for the treatment of idiopathic pulmonary arterial hypertension. Additional intriguing therapeutic properties are a protective effect on the myocardium through antihypertrophic and antiapoptotic mechanisms and on vascular function by improving endothelial responsiveness and tolerance to myocardial ischemia-reperfusion injury. These effects imply a potential usefulness in the treatment of coronary artery disease and heart failure. Evidence currently available for considering PDE5 inhibition an additional therapeutic opportunity in cardiovascular disorders is provided.
磷酸二酯酶是一类主要调节细胞内环核苷酸(如cGMP和cAMP)水平的蛋白质。磷酸二酯酶-5(PDE5)主要参与平滑肌细胞中cGMP的失活。最近,通过化学抑制PDE5,增加细胞内cGMP的可利用性,成为增强一氧化氮途径的一种有效的治疗选择。更具体地说,PDE5抑制似乎成功地用于治疗特发性肺动脉高压。其他有趣的治疗特性包括通过抗肥厚和抗凋亡机制对心肌的保护作用,以及通过改善内皮反应性和对心肌缺血-再灌注损伤的耐受性对血管功能的保护作用。这些作用表明其在治疗冠状动脉疾病和心力衰竭方面具有潜在用途。本文提供了目前可用于将PDE5抑制视为心血管疾病额外治疗机会的证据。