Researchers identify agent responsible for protection against early stages of atherosclerosis

Researchers from Boston University School of Medicine (BUSM) have identified for the first time the A2b adenosine receptor (A2bAR) as a possible new therapeutic target against atherosclerosis resulting from a diet high in fat and cholesterol. The findings, which appear on-line in Circulation, may have significant public health implications.

Adenosine is a metabolite produced naturally by cells at low levels, and at higher levels during exercise or stress. Adenosine binds to and activates , one of which is the A2bAR. Previous studies have described the A2bAR as anti-inflammatory and protective against kidney ischemia, cardiac reperfusion injury and restenosis, typically via bone marrow cell signals.

In mouse models, BUSM researchers found atherosclerosis induced by a high-fat diet was more pronounced in the absence of the A2bAR. They also found experiments indicated that A2bAR bone marrow cell signals alone were not sufficient to elicit this effect. "A2bAR genetic ablation led to elevated levels of liver and and triglycerides, and to fatty-liver pathology typical of steatosis, assessed by enzymatic assays and analysis of liver sections," explained senior author Katya Ravid, MD, a professor of medicine and biochemistry at BUSM.

The researchers also identified the mechanism underlying this effect in the liver, involving the control of the transcription factor SREBP-1 and its downstream targets-regulators of lipid synthesis. They found restoration of the A2bAR in the liver of A2bAR null mice reduced the lipid profile and atherosclerosis. "Most importantly, in vivo administration of a pharmacological activator of the A2bAR in on a high fat diet reduced lipid profile and atherosclerosis. Thus, this study provides the first evidence that the A2bAR regulates liver hyperlipidemia and atherosclerosis, suggesting that this receptor may be an effective against earlier stages of atherosclerosis," Ravid added.

Related Stories

'At-TRIB(1)-uting' a gene a new function in the liver

date Nov 15, 2010

Specific, relatively uncommon variations at a region of human chromosome 8 have recently been linked to fat (lipid) levels in the blood that decrease an individual's risk of atherosclerosis (a disease of the major arterial ...

Link found between immune system and high plasma lipid levels

date Apr 12, 2007

Researchers at the University of Chicago have found an unsuspected link between the immune system and high plasma lipid levels (cholesterol and triglycerides in the blood) in mice. The finding could lead to new ways to reduce ...

Recommended for you

A-fib recurrence common five years after ablation

date Apr 17, 2015

(HealthDay)—Most patients with atrial fibrillation (AF) and systolic heart failure who undergo ablation have AF recurrence at five years, according to a study published in the April issue of the Journal of ...

Applied physics helps decipher the causes of sudden death

date Apr 17, 2015

Sudden cardiac death accounts for approximately 10% of natural deaths, most of which are due to ventricular fibrillation. Each year, it causes 300,000 deaths in the United States and 20,000 in Spain. Researchers have demonstrated ...

Cognitive problems are common after cardiac arrest

date Apr 17, 2015

Half of all patients who survive a cardiac arrest experience problems with cognitive functions such as memory and attention. This has been shown by a major international study led from Lund University. Surprisingly, however, ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.