Minimally modified low-density lipoprotein upregulates the ETB and α1 receptors in mouse mesenteric arteries in vivo by activating the PI3K/Akt pathway

Abstract

Abstract Objectives The current study aimed to explore whether minimally modified low-density lipoprotein (mmLDL) via tail vein injection upregulates the ETB and α1 receptors in mouse mesenteric arteries by activating the PI3K/Akt pathway. Methods The contraction curves of the mesenteric arteries caused by sarafotoxin 6c (S6c, ETB receptor agonist) and phenylephrine (PE, α1 receptor agonist) were measured by a myograph system. Serum oxLDL was detected using enzyme-linked immunosorbent assays. The levels of the ETB receptor, the α1 receptor, PI3K, p-PI3K and p-Akt were detected using real-time polymerase chain reaction and Western blot analyses. Key findings Minimally modified low-density lipoprotein noticeably enhanced the contraction effect curves of S6c and PE, with significantly increased Emax values (P < 0.01), compared to those of the control group. This treatment significantly increased the mRNA expression and protein levels of the ETB and α1 receptors and the protein levels of p-PI3K and p-Akt in the vessel wall (P < 0.01). LY294002 inhibited the effect of mmLDL. Conclusions An increase in mmLDL activated the PI3K/Akt pathway, which upregulated the expression of the ETB and α1 receptors and enhanced the ETB and α1-receptor-mediated contractile function.