The role of intracellular 3'5'-cyclic adenosine monophosphate (cAMP) in atherosclerosis.
Intracellular cAMP is an ubiquitous intracellular second messenger that regulates important cellular functions. Intracellular cAMP levels are regulated by the enzymes adenylyl cyclase and phosphodiesterases. The role of cAMP in atherosclerosis is not widely accepted and incompletely characterized. Several reports support a role of cAMP in atherogenesis by modulating the function of vascular endothelium, the production of reactive oxygen species, the recruitment of circulating monocytes to the artery wall and their differentiation into macrophages- foam cells, by controlling the expression of pro- and anti-inflammatory interleukins, and regulating serum levels of triglycerides and cholesterol. Previous reports suggested an important role of cAMP in the modulation of atherosclerotic plaque progression by removal of excess free cholesterol from macrophages by inducing the ABCA1 secretory pathway and reducing circulating levels of cholesterol. Studies suggested a crucial role of cAMP on the development of acute coronary syndromes [(ACS); unstable angina, and acute myocardial infarction] and stroke, by modulating platelet aggregation and thrombus formation and the expression of metalloproteinases. This review focuses on the identified mechanisms and roles of cAMP in the prevention of atherosclerosis, atherogenesis, and progression of atherosclerosis and the development of ACS. Finally, it provides evidence that showed the beneficial effects that may derive from the inhibition of phosphodiesterase III and activation of adenylyl cyclase and subsequent elevation of cAMP levels. Thus, cAMP may be a possible target for the prevention and treatment of atherosclerosis.
Fantidis
Panayotis
P
Unidad de Angiología y Cirugía Vascular, Hospital San Pedro de Alcántara-Complejo Hospitalario de Cáceres, Cáceres, Comunidad Autónoma de Extremadura, Madrid, Spain. pfantidis@yahoo.es
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology; D000242:Cyclic AMP / Q000378:metabolism*; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology*
D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D008274:Magnesium