P2Y receptors and atherosclerosis in apolipoprotein E-deficient mice

摘要: Background and purpose:  P2Y nucleotide receptors are involved in the regulation of vascular tone, smooth muscle cell (SMC) proliferation inflammatory responses. The present study investigated whether they atherosclerosis. Experimental approach:  mRNA was quantified (RT-PCR) atherosclerotic plaque-free aorta segments apolipoprotein E-deficient (apoE–/–) mice. Macrophage activation assessed J774 macrophages, effects non-selective purinoceptor antagonists on atherosclerosis were evaluated cholesterol-fed apoE–/– mice. Key results:  P2Y6 receptor consistently elevated with atherosclerosis, whereas P2Y2 expression remained unchanged. Expression P2Y1 or P2Y4 low undetectable, not influenced by atherosclerosis. higher cultured macrophages than aortic SMCs. Furthermore, immunohistochemical staining plaques demonstrated P2Y6-positive but few SMCs, suggesting that macrophage recruitment accounted for increase during In contrast to ATP, P2Y6-selective agonist UDP increased activity inducible nitric oxide synthase interleukin-6 macrophages; this effect blocked suramin (100–300 µM) pyridoxal-phosphate-6-azophenyl-2′-4′-disulphonic acid (PPADS, 10–30 µM). Finally, 4-week treatment mice PPADS (50 25 mg·kg−1·day−1 respectively) reduced plaque size, without changing composition (relative SMC content) replication. Conclusions implications:  These results suggest involvement receptors, particularly warrant further research selective receptor-deficient