TY - JOUR
T1 - Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics
AU - Tsai, Emily J.
AU - Kass, David A.
PY - 2009/6
Y1 - 2009/6
N2 - Cyclic guanosine 3',5'-monophosphate (cGMP) mediates a wide spectrum of physiologic processes in multiple cell types within the cardiovascular system. Dysfunctional signaling at any step of the cascade - cGMP synthesis, effector activation, or catabolism - have been implicated in numerous cardiovascular diseases, ranging from hypertension to atherosclerosis to cardiac hypertrophy and heart failure. In this review, we outline each step of the cGMP signaling cascade and discuss its regulation and physiologic effects within the cardiovascular system. In addition, we illustrate how cGMP signaling becomes dysregulated in specific cardiovascular disease states. The ubiquitous role cGMP plays in cardiac physiology and pathophysiology presents great opportunities for pharmacologic modulation of the cGMP signal in the treatment of cardiovascular diseases. We detail the various therapeutic interventional strategies that have been developed or are in development, summarizing relevant preclinical and clinical studies.
AB - Cyclic guanosine 3',5'-monophosphate (cGMP) mediates a wide spectrum of physiologic processes in multiple cell types within the cardiovascular system. Dysfunctional signaling at any step of the cascade - cGMP synthesis, effector activation, or catabolism - have been implicated in numerous cardiovascular diseases, ranging from hypertension to atherosclerosis to cardiac hypertrophy and heart failure. In this review, we outline each step of the cGMP signaling cascade and discuss its regulation and physiologic effects within the cardiovascular system. In addition, we illustrate how cGMP signaling becomes dysregulated in specific cardiovascular disease states. The ubiquitous role cGMP plays in cardiac physiology and pathophysiology presents great opportunities for pharmacologic modulation of the cGMP signal in the treatment of cardiovascular diseases. We detail the various therapeutic interventional strategies that have been developed or are in development, summarizing relevant preclinical and clinical studies.
KW - Cardiovascular disease
KW - Natriuretic peptide receptor
KW - PKG
KW - Phosphodiesterases
KW - Soluble guanylyl cyclase
KW - cGMP
UR - http://www.scopus.com/inward/record.url?scp=67349149420&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67349149420&partnerID=8YFLogxK
U2 - 10.1016/j.pharmthera.2009.02.009
DO - 10.1016/j.pharmthera.2009.02.009
M3 - Review article
C2 - 19306895
AN - SCOPUS:67349149420
VL - 122
SP - 216
EP - 238
JO - Pharmacology and Therapeutics, Part A: Chemotherapy, Toxicology and
JF - Pharmacology and Therapeutics, Part A: Chemotherapy, Toxicology and
SN - 0163-7258
IS - 3
ER -