Department of Pharmacology and Physiology, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, United States.
Curr Opin Pharmacol. 2011 Dec;11(6):720-4. doi: 10.1016/j.coph.2011.09.002. Epub 2011 Sep 29.
Pathological vascular remodeling is a hallmark of most vascular disorders such as atherosclerosis, postangioplasty restenosis, allograft vasculopathy, and pulmonary hypertension. Pathological vascular remodeling is a multi-cell-dependent process leading to detrimental changes of vessel structure and eventual vessel occlusion. Cyclic nucleotide signaling regulates a variety of vascular functions ranging from cell contractility to cell growth. Cyclic nucleotide phosphodiesterases (PDEs), a large family of structurally and functionally distinct isozymes, regulate cyclic nucleotide levels and compartmentalization through catalyzing their degradation reaction. Increasing evidence has suggested that one of the important mechanisms for specific cyclic nucleotide regulation is exerted through selective activation or inhibition of distinct PDE isozymes. This review summarizes the work done to characterize the role and therapeutic potential of PDE1 isozymes in pathological vascular remodeling.
病理性血管重构是大多数血管疾病的标志，如动脉粥样硬化、血管成形术后再狭窄、同种异体移植物血管病和肺动脉高压。病理性血管重构是一个多细胞依赖的过程，导致血管结构的有害变化，并最终导致血管闭塞。环核苷酸信号转导调节多种血管功能，从细胞收缩力到细胞生长。环核苷酸磷酸二酯酶（PDEs）是一个结构和功能上明显不同的同工酶大家族，通过催化其降解反应来调节环核苷酸水平和区室化。越来越多的证据表明，特定环核苷酸调节的一个重要机制是通过选择性激活或抑制不同的 PDE 同工酶来实现的。这篇综述总结了对 PDE1 同工酶在病理性血管重构中的作用和治疗潜力进行表征的工作。
