title: A₁ adenosine receptor deficiency or inhibition reduces atherosclerotic lesions in apolipoprotein E deficient mice.
abstract: OBJECTIVE
  The goal of this study was to determine whether the A1 adenosine receptor (AR) plays a role in atherosclerosis development and to explore its potential mechanisms.
  
  
  RESULTS
  Double knockout (DKO) mice, deficient in the genes encoding A1 AR and apolipoprotein E (apoE), demonstrated reduced atherosclerotic lesions in aortic arch (en face), aortic root, and innominate arteries when compared with apoE-deficient mice (APOE-KO) of the same age. Treating APOE-KO with an A1 AR antagonist (DPCPX) also led to a concentration-dependent reduction in lesions. The total plasma cholesterol and triglyceride levels were not different between DKO and APOE-KO; however, higher triglyceride was observed in DKO fed a high-fat diet. DKO also had higher body weights than APOE-KO. Plasma cytokine concentrations (IL-5, IL-6, and IL-13) were significantly lower in DKO. Proliferating cell nuclear antigen expression was also significantly reduced in the aorta from DKO. Despite smaller lesions in DKO, the composition of the innominate artery lesion and cholesterol loading and efflux from bone marrow-derived macrophages of DKO were not different from APOE-KO.
  
  
  CONCLUSIONS
  The A1 AR may play a role in the development of atherosclerosis, possibly due to its pro-inflammatory and mitogenic properties.
authors: Department of Physiology and Pharmacology, Center for Cardiovascular and Respiratory Sciences, West Virginia University, 1 Medical Center Drive, Morgantown, WV, USA.
authors: Bunyen
authors: B
authors: Teng
authors: Jonathan D
authors: JD
authors: Smith
authors: Michael E
authors: ME
authors: Rosenfeld
authors: Peggy
authors: P
authors: Robinet
authors: Mary E
authors: ME
authors: Davis
authors: R Ray
authors: RR
authors: Morrison
authors: S Jamal
authors: SJ
authors: Mustafa
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043682:Receptor, Adenosine A1 / Q000172:deficiency / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D043682:Receptor, Adenosine A1; D002784:Cholesterol
keywords: 1,3-Dipropyl-8-cyclopentylxanthine (DPCPX); A1 adenosine receptor; Apolipoprotein E; Cytokines; IL-13