期刊
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
卷 467, 期 2, 页码 415-427出版社
SPRINGER
DOI: 10.1007/s00424-014-1503-5
关键词
Heme oxygenase; Carbon monoxide; Calcium channel; Proliferation; Vascular smooth muscle
类别
资金
- British Heart Foundation
- British Heart Foundation [FS/12/42/29585, FS/14/41/30955, FS/10/010/28169, PG/13/61/30410] Funding Source: researchfish
Induction of the antioxidant enzyme heme oxygenase-1 (HO-1) affords cellular protection and suppresses proliferation of vascular smooth muscle cells (VSMCs) associated with a variety of pathological cardiovascular conditions including myocardial infarction and vascular injury. However, the underlying mechanisms are not fully understood. Over-expression of Ca(v)3.2 T-type Ca2+ channels in HEK293 cells raised basal [Ca2+](i) and increased proliferation as compared with non-transfected cells. Proliferation and [Ca2+](i) levels were reduced to levels seen in non-transfected cells either by induction of HO-1 or exposure of cells to the HO-1 product, carbon monoxide (CO) (applied as the CO releasing molecule, CORM-3). In the aortic VSMC line A7r5, proliferation was also inhibited by induction of HO-1 or by exposure of cells to CO, and patch-clamp recordings indicated that CO inhibited T-type (as well as L-type) Ca2+ currents in these cells. Finally, in human saphenous vein smooth muscle cells, proliferation was reduced by T-type channel inhibition or by HO-1 induction or CO exposure. The effects of T-type channel blockade and HO-1 induction were non-additive. Collectively, these data indicate that HO-1 regulates proliferation via CO-mediated inhibition of T-type Ca2+ channels. This signalling pathway provides a novel means by which proliferation of VSMCs (and other cells) may be regulated therapeutically.
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