The Influence of Human CETP on Endothelium-Dependent Relaxation of Aorta

The Influence of Human CETP on Endothelium-Dependent Relaxation of Aorta

• Autor
• Carolina Martins Lazaro
• Co-autores
• Helena Coutinho Franco de Oliveira , Ana Paula Davel
• Resumo

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  The cholesteryl ester transfer protein (CETP) main function is to transfer the cholesterol from HDL to lipoproteins containing apolipoprotein B (VLDL+LDL). Because it reduces HDL-cholesterol, CETP has been considered atherogenic and its inhibition a target for pharmacological studies. However, the role of CETP on the vasculature function is unknown. Thus, the aim of this study is to analyze the influence of CETP expression on the endothelium vasodilatory function. For this, we used male and female (4-5-month-old) human CETP transgenic mice (hCETP) and the respective nontransgenic littermates (NTg), treated or not with an atherogenic diet (22 and 0.15% fat and cholesterol respectively) for 8 weeks (Ethical protocol # 5353-1/2019). Systolic blood pressure (SBP) was measured by plethysmography and thoracic aorta was isolated. Endothelium-dependent relaxation to acetylcholine was evaluated in aortic rings in the presence and absence of the NOS inhibitor L-NAME. We observed that SBP was increased in female hCETP mice compared with female NTg, effect that was not observed in males. The acetylcholine-induced relaxation was not significantly modified either in male or female hCETP mice compared with respective NTg. Interestingly, the cholesterol-rich diet increased the acetylcholine-induced relaxation in aorta from male hCETP mice, associated with an increased effect of L-NAME, suggesting an elevated NOS participation. The effect of the atherogenic diet on female hCETP mice is under analysis. The preliminary data suggest that a high-cholesterol diet increases NOS contribution to aortic endothelium-dependent relaxation in male mice overexpressing human CETP. Next, we intend to investigate the mechanisms involved in such effect and a possible sexual dimorphism in the role of vascular CETP.

   

• Palavras-chave
• CETP, Vascular Reactivity, Blood Pressure, Endothelium
• Modalidade
• Pôster
• Área Temática
• Disfunção endotelial