Minimally modified LDL upregulates endothelin type A receptors in rat coronary arterial smooth muscle cells

Abstract

Minimally modified low-density lipoprotein (mmLDL) is a risk factor for cardiovascular disease. The present study investigated the effects of mmLDL on the expression of endothelin type A (ET A) receptors in coronary arteries. Rat coronary arteries were organ-cultured for 24 h. The contractile responses were recorded using a myographic system. ET A receptor mRNA and protein expressions were determined using real-time PCR and western blotting, respectively. The results showed that organ-culturing in the presence of mmLDL enhanced the arterial contractility mediated by the ET A receptor in a concentration- dependent and time-dependent manner. Culturing with mmLDL (10 g/mL) for 24 h shifted the concentration-contractile curves toward the left significantly with increased E max of 228 % ± 20 % from control of 100 % ± 10 % and significantly increased ET A receptor mRNA and protein levels. Inhibition of the protein kinase C, extracellular signal-related kinases 1 and 2 (ERK1/2), or NF-B activities significantly attenuated the effects of mmLDL. The c-Jun N-terminal kinase inhibitor or the p38 pathway inhibitor, however, had no such effects. The results indicate that mmLDL upregulates the ET A receptors in rat coronary arterial smooth muscle cells mainly via activating protein kinase C, ERK1/2, and the downstream transcriptional factor, NF-B. © 2013 Jie Li et al.