磷酸二酯酶的心血管功能调节作用

Phosphodiesterase Regulation of Cardiovascular Functions

磷酸二酯酶(phosphodiesterase,PDE)是细胞内第二信使cAMP和cGMP降解的关键酶,作为药物研发的靶点受到广泛关注。近年研究发现,PDE在心肌细胞中能与β-肾上腺素受体及一些与兴奋收缩相关的蛋白形成复合物而使细胞内信号传递区室化分布,该现象可能为PDE抑制剂治疗慢性心力衰竭提供新的启示。血管平滑肌功能调节主要为血管张力和表型的调控,PDE5抑制剂舒张血管的作用已成功应用到勃起障碍的治疗。PDE4和PDE1C等在增殖的平滑肌细胞中表达量增高,单独抑制PDE的某一亚型将为治疗与平滑肌增殖有关的疾病(如肺动脉高压、血管成行术后再狭窄)提供新的途径。本文将重点阐述近年来PDE在心血管系统功能调节研究中的主要进展,以及PDE抑制剂在心血管系统疾病治疗中的应用。

Phosphodiesterases （PDEs） are the enzymes to degrade the intracellular second messengers cAMP and cGMP. They are the targets for drug research and development of great therapeutic interests. Recent studies show that PDEs in cardiomyocytes form a complex with β-adrenergic receptor and related proteins to ensure precise and localized cAMP signaling. The mechanism may provide new insight for the treatment of chronic heart failure with PDE inhibitors. The functions of blood vessels are regulated by the reactivity and phenotypes of vascular smooth muscle. PDE5 inhibitors, by enhancing the vasodilator effect of cGMP, have been successfully applied to the treatment of erectile dysfunction. The expression of PDE4 and PDE1C is upregulated during proliferation of vascular smooth muscle cells. Selectively inhibiting these PDE subtypes may provide a new way in treating disorders associated with vascular proliferation such as pulmonary hypertension and post - angioplasty restenosis. This review will focus on recent advance in PDE regulation of cardiovascular functions and new applications of PDE inhibitors in cardiovas-cular diseases.