Regulation of gene expression by cyclic GMP.
Cyclic GMP, produced in response to nitric oxide and natriuretic peptides, is a key regulator of vascular smooth muscle cell contractility, growth, and differentiation, and is implicated in opposing the pathophysiology of hypertension, cardiac hypertrophy, atherosclerosis, and vascular injury/restenosis. cGMP regulates gene expression both positively and negatively at transcriptional as well as at posttranscriptional levels. cGMP-regulated transcription factors include the cAMP-response element binding protein CREB, the serum response factor SRF, and the nuclear factor of activated T cells NF/AT. cGMP can regulate CREB directly, through phosphorylation by cGMP-dependent protein kinase, or indirectly, through activation of mitogen-activated protein kinase pathways; regulation of SRF and NF/AT by cGMP is indirect, through modulation of RhoA and calcineurin signaling, respectively. Downregulation of the RNA-binding protein HuR by cGMP leads to destabilization of guanylate cyclase mRNA, but this posttranscriptional mechanism may affect many more cGMP-regulated genes. In this review, we discuss the role of cGMP-regulated gene expression in (patho)physiological processes most relevant to the cardiovascular system, such as regulation of vascular tone, cardiac hypertrophy, phenotypic modulation of vascular smooth muscle cells, and regulation of cell proliferation and apoptosis.
Pilz
Renate B
RB
Department of Medicine and Cancer Center, University of California at San Diego, 9500 Gilman Dr, La Jolla, Calif 92093-0652, USA. rpilz@ucsd.edu
Casteel
Darren E
DE
D000818:Animals; D006332:Cardiomegaly / Q000503:physiopathology; D006152:Cyclic GMP / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D014666:Vasomotor System / Q000502:physiology
D014157:Transcription Factors; D006162:Guanylate Cyclase; D006152:Cyclic GMP