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.
Keywords: atherogenesis; atherosclerotic plaque; cAMP; epidemiological and clinical evidence; therapeutic implications
Document Type: Research Article
Publication date: 01 July 2010
- Vascular disease is the commonest cause of death in Westernized countries and its incidence is on the increase in developing countries. It follows that considerable research is directed at establishing effective treatment for acute vascular events. Long-term treatment has also received considerable attention (e.g. for symptomatic relief). Furthermore, effective prevention, whether primary or secondary, is backed by the findings of several landmark trials.
Vascular disease is a complex field with primary care physicians and nurse practitioners as well as several specialties involved. The latter include cardiology, vascular and cardio thoracic surgery, general medicine, radiology, clinical pharmacology and neurology (stroke units). Current Vascular Pharmacology will publish reviews to update all those concerned with the treatment of vascular disease. For example, reviews commenting on recently published trials or new drugs will be included. In addition to clinically relevant topics we will consider 'research-based' reviews dealing with future developments and potential drug targets. Therefore, another function of Current Vascular Pharmacology is to bridge the gap between clinical practice and ongoing research.
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