Regulation of Gene Expression by Cyclic GMP

• Published in: Circulation research Vol. 93; no. 11; pp. 1034 - 1046
• Main Authors: Pilz, Renate B, Casteel, Darren E
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 28-11-2003; Lippincott; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: Animals; Biological and medical sciences; Blood vessels and receptors; Cardiomegaly - physiopathology; Cyclic GMP - metabolism; Cyclic GMP - physiology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - physiology; Guanylate Cyclase - metabolism; Humans; MAP Kinase Signaling System - physiology; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - physiology; RNA Processing, Post-Transcriptional - physiology; Signal Transduction - physiology; Transcription Factors - metabolism; Vasomotor System - physiology; Vertebrates: cardiovascular system; Human; Stability; Transcription; cyclic GMP; 3',5'-GMP; Smooth muscle; Review; Gene expression; Genetic translation; Regulation(control); Messenger RNA; Animal; Blood vessel; translation; Circulatory system; mRNA stability
• DOI: 10.1161/01.RES.0000103311.52853.48
• EISSN: 1524-4571
• ISSN: 0009-7330

ABSTRACT—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.