期刊
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
卷 456, 期 5, 页码 769-785出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00424-008-0491-8
关键词
vascular smooth muscle cell proliferation; phenotypic switching; Ca2+ signaling; canonical transient receptor potential channels; L-type and T-type voltage-dependent Ca2+ channels; membrane potential; potassium channels; Ca2+/calmodulin-dependent protein kinase II (CaMKII)
类别
资金
- NHLBI NIH HHS [R01 HL049426, R01 HL-4942612] Funding Source: Medline
- NIEHS NIH HHS [K22 ES014729, K22 ES014729-02, K22ES014729] Funding Source: Medline
Calcium (Ca2+) is a highly versatile second messenger that controls vascular smooth muscle cell (VSMC) contraction, proliferation, and migration. By means of Ca2+ permeable channels, Ca2+ pumps and channels conducting other ions such as potassium and chloride, VSMC keep intracellular Ca2+ levels under tight control. In healthy quiescent contractile VSMC, two important components of the Ca2+ signaling pathways that regulate VSMC contraction are the plasma membrane voltage-operated Ca2+ channel of the high voltage-activated type (L-type) and the sarcoplasmic reticulum Ca2+ release channel, Ryanodine Receptor (RyR). Injury to the vessel wall is accompanied by VSMC phenotype switch from a contractile quiescent to a proliferative motile phenotype (synthetic phenotype) and by alteration of many components of VSMC Ca2+ signaling pathways. Specifically, this switch that culminates in a VSMC phenotype reminiscent of a non-excitable cell is characterized by loss of L-type channels expression and increased expression of the low voltage-activated (T-type) Ca2+ channels and the canonical transient receptor potential (TRPC) channels. The expression levels of intracellular Ca2+ release channels, pumps and Ca2+-activated proteins are also altered: the proliferative VSMC lose the RyR3 and the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase isoform 2a pump and reciprocally regulate isoforms of the Ca2+/calmodulin-dependent protein kinase II. This review focuses on the changes in expression of Ca2+ signaling proteins associated with VSMC proliferation both in vitro and in vivo. The physiological implications of the altered expression of these Ca2+ signaling molecules, their contribution to VSMC dysfunction during vascular disease and their potential as targets for drug therapy will be discussed.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据