A Mouse Model of Hypercholesterolemia-Induced Erectile Dysfunction

Abstract

Hypercholesterolemia is one of the most important risk factors for the development of erectile dysfunction (ED) in men. We employed an established mouse model of hypercholesterolemia. We test for abnormalities in vasoreactivity in corporal tissue and temporally correlated changes in vasoreactivity with alterations in histology and protein expression. A total of 150 mice were studied. A total of 100 apolipoprotein-E knockout (ApoE(-/-)) mice were fed a 1.25% cholesterol diet for 2, 4, 8, and 12 weeks (N = 25/group), while a group of ApoE(-/-) and wild-type Bl-6 mice were fed a normal diet. The study was terminated, and all mice were harvested at 22 weeks of age for vasoreactivity, histology, and protein studies from corporal tissues. Dose-response curves were generated to evaluate endothelium-dependent and endothelium-independent vasoreactivity, ex vivo. The contents of endothelial cells, smooth muscle cells, and smooth muscle/collagen ratio were assessed by immunohistochemistry staining or Masson staining. Level of cyclic guanosine monophosphate (cGMP) was detected by enzyme immunoassay assay. Levels of phosphorylated endothelial nitric oxide synthase (p-eNOS)/total eNOS, neuronal nitric oxide synthase (nNOS), and cyclic GMP-dependent kinase (cGK-1) protein were assessed by Western analysis. Abnormalities in endothelium-dependent and endothelium-independent vasoreactivities, endothelial content, smooth muscle/collagen ratio, p-eNOS phosphorylation at Ser1177 only, nNOS, cGMP, and cGK-1 changed with the different durations of the high-cholesterol diet. These data demonstrate that this mouse model is suitable for investigating aspects of hypercholesterolemic ED.