Abstract 343: Inactivation of the P2Y2 Receptor Gene Reduces Atherosclerosis

Autor: Cheikh Seye, Yucksel Agca, Shaomin Qian
Rok vydání: 2012
Předmět:
Zdroj: Circulation Research. 111
ISSN: 1524-4571
0009-7330
DOI: 10.1161/res.111.suppl_1.a343
Popis: Rationale: Nucleotides acting via P2Y 2 nucleotide receptors (P2Y 2 R) regulate both migration of vascular smooth muscle cells and endothelial recruitment of monocyte/macrophage in vivo. Objective: We aimed to determine whether inactivation of the P2Y 2 R gene protects against neointima hyperplasia and atherosclerosis. Method and results: We performed femoral artery cuff injury in wild-type and P2Y 2 R -/- mice and examined neointima formation 14 days after injury, the time corresponding to peak SMC accumulation in this model. Wild-type mice exhibited a 190% increase in cellular proliferation ( P P =0.010) compared to wild-type mice. There was no significant difference in the medial area between wild type and P2Y 2 R -/- mice. To assess the contribution of P2Y 2 R to atherosclerosis, we first generated P2Y 2 R -/- /ApoE -/- mice by mating ApoE -/- mice with P2Y 2 R -/- mice. We then examined the development of atherosclerotic lesions 30 weeks after mice were fed with standard chow diet, the time corresponding to widespread atherosclerotic lesions in the ApoE -/- mouse model. P2Y 2 R -/- /ApoE -/- and ApoE -/- exhibited no differences in blood pressure, number of circulating leukocytes, differential counts, or total blood cholesterol. The surface covered by atherosclerotic lesions in the entire aorta was significantly reduced in P2Y 2 R -/- /ApoE -/- mice as compared to ApoE -/- . The total intimal lesion area in the aortic sinus was significantly less in P2Y 2 R -/- /ApoE -/- mice than in ApoE -/- mice. Mac-3 staining revealed a significant reduction in the percentage of total plaque area occupied by macrophages in P2Y 2 R -/- /ApoE -/- mice compared with Apo E -/- mice. Conclusion: These findings suggest that unraveling the molecular mechanisms associated with P2Y 2 R may lead to potential drug targets for the treatment of coronary syndromes and percutaneous coronary interventions.
Databáze: OpenAIRE
Externí odkaz: