Regulation of vascular smooth muscle cell phenotype by cyclic GMP and cyclic GMP-dependent protein kinase.
This basic science review examines the role of cGMP and cGMP-dependent protein kinase (PKG) in the regulation of vascular smooth muscle cell (VSMC) phenotype. The first such studies suggested a role for nitric oxide (NO) and atrial natriuretic peptides (ANP), and the downstream second messenger cGMP, in the inhibition of VSMC proliferation. Subsequently, many laboratories confirmed the anti-proliferative effects of the cGMP pathway in cultured cells and the anti-atherosclerotic effects of the pathway in in vivo animal models. Other studies suggested that the cGMP target, PKG, mediated the anti-proliferative effects of cGMP although other laboratories have not consistently observed these effects. On the other hand, PKG mediates cGMP-dependent increases in smooth muscle-specific gene expression, and in vivo studies suggest that PKG expression itself reduces vascular lesions. The mechanisms by which PKG regulates gene expression are addressed, but it still unknown how the cGMP-PKG pathway is involved in smooth muscle-specific gene expression and phenotype.
Lincoln
Thomas M
TM
Department of Physiology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA. tlincoln@usouthal.edu
Wu
Xing
X
Sellak
Hassan
H
Dey
Nupur
N
Choi
Chung-Sik
CS
D000199:Actins / Q000737:chemistry; D000818:Animals; D001011:Aorta / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000737:chemistry; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000737:chemistry; D002148:Calmodulin-Binding Proteins / Q000737:chemistry; D049109:Cell Proliferation; D003094:Collagen / Q000737:chemistry; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000737:chemistry* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008840:Microfilament Proteins / Q000737:chemistry; D008954:Models, Biological; D009130:Muscle, Smooth / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism; D009569:Nitric Oxide / Q000737:chemistry; D010641:Phenotype; D010958:Plasminogen / Q000737:chemistry; D011487:Protein Conformation; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism; D015398:Signal Transduction; D000096985:Calponins
D000199:Actins; D009320:Atrial Natriuretic Factor; D002135:Calcium-Binding Proteins; D002148:Calmodulin-Binding Proteins; D003094:Collagen; D006152:Cyclic GMP; D017869:Cyclic GMP-Dependent Protein Kinases; D016023:Integrins; D008840:Microfilament Proteins; D009218:Myosins; D009569:Nitric Oxide; D010958:Plasminogen; D016271:Proto-Oncogene Proteins c-myc; D011945:Receptors, Angiotensin; D000096985:Calponins