Apolipoprotein B of low-density lipoprotein impairs nitric oxide-mediated endothelium-dependent relaxation in rat mesenteric arteries

作者：Zhang Yaping; Zhang Wei; Edvinsson Lars; Xu Cang Bao^*

来源：European Journal of Pharmacology, 2014, 725: 10-17.

DOI：10.1016/j.ejohar.2014.01.008

• Apolipoprotein B
• Low-density lipoprotein
• Endothelial dysfunction
• Vasodilation
• Lipid peroxidation
• Cardiovascular disease

Apolipoprotein B (ApoB) of low-density lipoprotein (LDL) causes endothelial dysfunction in the initial stage of atherogenesis. The present study was designed to explore the underlying molecular mechanisms involved. Rat mesenteric arteries were organ cultured in the presence of different concentrations of ApoB or LDL. Vasodilation induced by acetylcholine was monitored by a sensitive myograph. Nitric oxide (NO), endothelium-dependent hyperpolarizing factor (EDHF) and prostacyclin (PGI(2)) pathways were characterized by using specific pathway inhibitors. Real-time PCR and immunohistochemistry with confocal microscopy were used to examine alteration of mRNA and protein expressions for NO synthases (eNOS and iNOS) and cycloxygenase (COX), respectively. Lipid peroxidation was measured by thiobarbituric acid reactive substances. In the presence of either LDL or ApoB for 24 h concentration-dependently attenuated the endothelium-dependent vasodilation. Immunohistochemistry staining of endothelial cell marker CD31 was weaker in the presence of LDL, indicating that LDL induced damage to the endothelium. Using the pathway specific inhibitors demonstrated that LDL-induced impairing vasoclilanon was mainly due to attenuation of NO pathway. This was supported by decreasing mRNA (real-time PCR) and protein expression (immunohistochemistry) for eNOS and iNOS, but not COX, in the presence of LDL. In addition, the levels of lipid peroxidation significantly increased in the presence of LDL for 24 h. In conclusion, ApoB of LDL impairs vasodilation with damaging the endothelium and attenuating the NO mediated endothelium dependent relaxation, which might associate with lipid peroxidation and contribute to the development of cardiovascular disease.

• 出版日期2014-2-15
• 单位西安医学院