Affiliation:
1. From the Department of Medicine and Winthrop Research Institute, Winthrop-University Hospital, Mineola, NY (A.B.R.); Division of Translational Medicine, Department of Medicine, New York University School of Medicine, New York, NY (B.N.C.).
Abstract
Macrophages rely on reverse cholesterol transport mechanisms to rid themselves of excess cholesterol. By reducing accumulation of cholesterol in the artery wall, reverse cholesterol transport slows or prevents development of atherosclerosis. In stable macrophages, efflux mechanisms balance influx mechanisms, and accumulating lipids do not overwhelm the cell. Under atherogenic conditions, inflow of cholesterol exceeds outflow, and the cell is ultimately transformed into a foam cell, the prototypical cell in the atherosclerotic plaque. Adenosine is an endogenous purine nucleoside released from metabolically active cells by facilitated diffusion and generated extracellularly from adenine nucleotides. Under stress conditions, such as hypoxia, a depressed cellular energy state leads to an acute increase in the extracellular concentration of adenosine. Extracellular adenosine interacts with 1 or more of a family of G protein–coupled receptors (A
1
, A
2A
, A
2B
, and A
3
) to modulate the function of nearly all cells and tissues. Modulation of adenosine signaling participates in regulation of reverse cholesterol transport. Of particular note for the development of atherosclerosis, activation of A
2A
receptors dramatically inhibits inflammation and protects against tissue injury. Potent antiatherosclerotic effects of A
2A
receptor stimulation include inhibition of macrophage foam cell transformation and upregulation of the reverse cholesterol transport proteins cholesterol 27-hydroxylase and ATP binding cassette transporter A1. Thus, A
2A
receptor agonists may correct or prevent the adverse effects of inflammatory processes on cellular cholesterol homeostasis. This review focuses on the importance of extracellular adenosine acting at specific receptors as a regulatory mechanism to control the formation of foam cells under conditions of lipid loading.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Reference96 articles.
1. Endocardial and epicardial interstitial purines and lactate during graded ischemia;Delyani JA;Am J Physiol,1994
2. Adenosine receptor-mediated cardioprotection: are all 4 subtypes required or redundant?;McIntosh VJ;J Cardiovasc Pharmacol Ther,2011
3. Adenosine receptors: therapeutic aspects for inflammatory and immune diseases
4. Adenosine Blocks IFN-γ-Induced Phosphorylation of STAT1 on Serine 727 to Reduce Macrophage Activation
5. Gamma interferon: a central mediator in atherosclerosis
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