A(1) adenosine receptor deficiency or inhibition reduces atherosclerotic lesions in apolipoprotein E deficientmice

作者：Teng Bunyen^*; Smith Jonathan D; Rosenfeld Michael E; Robinet Peggy; Davis Mary E; Morrison R Ray; Mustafa S Jamal

来源：Cardiovascular Research, 2014, 102(1): 157-165.

DOI：10.1093/cvr/cvu033

• A(1) adenosine receptor
• Apolipoprotein E
• Cytokines
• 1,3-Dipropyl-8-cyclopentylxanthine (DPCPX)
• IL-13

Aims The goal of this study was to determine whether the A(1) adenosine receptor (AR) plays a role in atherosclerosis development and to explore its potential mechanisms. %26lt;br%26gt;Methods and results Double knockout (DKO) mice, deficient in the genes encoding A(1) 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 A(1) 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. %26lt;br%26gt;Conclusion The A(1) AR may play a role in the development of atherosclerosis, possibly due to its pro-inflammatory and mitogenic properties.

• 出版日期2014-4-1