Abstract
Minimally modified low-density lipoprotein (mmLDL) is a well-known risk factor for cardiovascular diseases. The present study was designed to investigate the role of mmLDL in the endothelium-dependent relaxation of mouse mesenteric arteries. A sensitive myograph system was employed to examine the endothelial function of mesenteric arteries. mRNA and protein expression levels were determined using real-time PCR and Western blotting, respectively. The ultramicrostructure of mesenteric vascular beds was investigated using a transmission electron microscope. The results showed that mmLDL significantly impaired the acetylcholine-induced (3 × 10−<sup>10</sup> to 1 × 10−<sup>4</sup><smlcap>M</smlcap>) endothelium-dependent relaxation of mouse mesenteric arteries with markedly reduced pIC<sub>50</sub> (p < 0.05) and R<sub>max</sub> values (p < 0.001). In addition, mmLDL increased the levels of superoxide production and nitrotyrosine concentration and impaired the endothelial microstructure with decreased K<sub>Ca</sub>3.1 and K<sub>Ca</sub>2.3 expression. In conclusion, mmLDL increases superoxide and nitrotyrosine levels, damages endothelial microstructure with decreased K<sub>Ca</sub>3.1 and K<sub>Ca</sub>2.3 expression, and ultimately attenuates relaxation mediated by nitric oxide- and endothelium-derived hyperpolarizing factor.
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