Altered Angiogenic Growth Factor-Akt-eNOS Signal Pathway May Play an Important Role in the Deterioration of Erectile Function in a Rat Model of Hypercholesterolemia

초록

Purpose: This study focuses on the expression of angiogenic growth factors and their downstream target molecules, phosphatidylinositol 3-kinase (PI3-kinase)-Akt-endothelial nitric oxide synthase (eNOS) signaling axis, that are potentially involved in blood vessel growth and homeostasis in a corpus cavernosum of hypercholesterolemic rat. Materials and Methods: Forty-eight 2-month-old male Sprague-Dawley rats were subjected in this study. The control animal (n=24) was fed a normal diet and the experimental one (n=24) was fed 4% cholesterol and 1% cholic acid diet for 3 months. At 5 months serum lipid level was measured in all animals. After electrostimulation of cavernous nerve penile tissue was collected for immunohistochemistry (n=12, respectively). Cavernous expressions of vascular endothelial growth factor (VEGF), angiopoietins, tie2 receptor, PI3-kinase, Akt/phospho-Akt (pAkt) and eNOS/phospho-eNOS (peNOS) genes or proteins were also evaluated (n=12, respectively). Results: Total cholesterol level was significantly increased in hypercholesterolemic group compared to those in control (p<0.01). Electrostimulation of the cavernous nerve revealed that the ratio of maximal intracavernous pressure to systemic arterial pressure (mICP/SAP) was significantly lower in hypercholesterolemic group than control (p<0.01). Cavernous expression of VEGF, angiopoietin-1, -2, genes and proteins were decreased in cholesterol group than in controls. Akt/pAkt and eNOS/peNOS protein expression in cholesterol group were also decreased compared to controls. Endothelial cell content was significantly decreased in rats fed a cholesterol diet compared to normal diet group (p<0.01). Conclusions: We think the finding of decreased amount of angiogenic growth factor-Akt/pAkt-eNOS/peNOS in corpus cavernosum may play a major role in the endothelial cell dysfunction and subsequent deterioration of erectile function in hypercholesterolemic rats.