• PMID: 28923309
• Gene Name: CAV1
• Condition: DM-related erectile dysfunction, Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: DM-related erectile dysfunction, Male infertility

Altered Penile Caveolin Expression in Diabetes: Potential Role in Erectile Dysfunction

Parikh J, Zemljic-Harpf A, Fu J, Giamouridis D, Hsieh TC, Kassan A, Murthy KS, Bhargava V, Patel HH, Rajasekaran MR.

BACKGROUND: The pathophysiology of increased severity of erectile dysfunction in men with diabetes and their poor response to oral pharmacotherapy are unclear. Defective vascular endothelium and consequent impairment in the formation and action of nitric oxide (NO) are implicated as potential mechanisms. Endothelial NO synthase, critical for NO generation, is localized to caveolae, plasma membrane lipid rafts enriched in structural proteins, and caveolins. Type 2 diabetes mellitus (T2DM)-induced changes in caveolin expression are recognized to play a role in cardiovascular dysfunction. AIMS: To evaluate DM-related changes to male erectile tissue in a mouse model that closely resembles human T2DM and study the specific role of caveolins in penile blood flow and microvascular perfusion using mice lacking caveolin (Cav)-1 or Cav-3. METHODS: We used wild-type C57BL6 (control) and Cav-1 and Cav-3 knockout (KO) male mice. T2DM was induced by streptozotocin followed by a high-fat diet for 4 months. Penile expressions of Cav-1, Cav-3, and endothelial NO synthase were determined by western blot, and phosphodiesterase type 5 activity was measured using [(3)H] cyclic guanosine monophosphate as a substrate. For hemodynamic studies, Cav-1 and Cav-3 KO mice were anesthetized, and penile blood flow (peak systolic velocity and end-diastolic velocity; millimeters per second) was determined using a high-frequency and high-resolution digital imaging color Doppler system. Penile tissue microcirculatory blood perfusion (arbitrary perfusion units) was measured using a novel PeriCam PSI system. OUTCOMES: Penile erectile tissues were harvested for histologic studies to assess Cav-1, Cav-3, and endothelial NO synthase expression, phosphodiesterase type 5 activity, and blood flow, and perfusion measurements were assessed for hemodynamic studies before and after an intracavernosal injection of prostaglandin E(1) (50 ng). RESULTS: In T2DM mice, decreased Cav-1 and Cav-3 penile protein expression and increased phosphodiesterase type 5 activity were observed. Decreased response to prostaglandin E(1) in peak systolic velocity (33 ± 4 mm/s in Cav-1 KO mice vs 62 ± 5 mm/s in control mice) and perfusion (146 ± 12 AU in Cav-1 KO mice vs 256 ± 12 AU in control mice) was observed. Hemodynamic changes in Cav-3 KO mice were insignificant. CLINICAL TRANSLATION: Our findings provide novel mechanistic insights into erectile dysfunction severity and poor pharmacotherapy that could have potential application to patients with T2DM. STRENGTHS AND LIMITATIONS: Use of KO mice and novel hemodynamic techniques are the strengths. A limitation is the lack of direct evaluation of penile hemodynamics in T2DM mice. CONCLUSION: Altered penile Cav-1 expression in T2DM mice and impaired penile hemodynamics in Cav-1 KO mice suggests a regulatory role for Cav-1 in DM-related erectile dysfunction. Parikh J, Zemljic-Harpf A, Fu J, et al. Altered Penile Caveolin Expression in Diabetes: Potential Role in Erectile Dysfunction. J Sex Med 2017;14:1177-1186. CI - Published by Elsevier Inc. FAU - Parikh, Jay AU - Parikh J AD - Department of Surgery, University of California-San Diego and San Diego VA Healthcare System, San Diego, CA, USA. FAU - Zemljic-Harpf, Alice AU - Zemljic-Harpf A AD - Department of Anesthesiology, University of California-San Diego and San Diego VA Healthcare System, San Diego, CA, USA. FAU - Fu, Johnny AU - Fu J AD - Department of Surgery, University of California-San Diego and San Diego VA Healthcare System, San Diego, CA, USA. FAU - Giamouridis, Dimosthenis AU - Giamouridis D AD - Department of Internal Medicine, University of California-San Diego and San Diego VA Healthcare System, San Diego, CA, USA. FAU - Hsieh, Tung-Chin AU - Hsieh TC AD - Department of Surgery, University of California-San Diego and San Diego VA Healthcare System, San Diego, CA, USA. FAU - Kassan, Adam AU - Kassan A AD - Department of Anesthesiology, University of California-San Diego and San Diego VA Healthcare System, San Diego, CA, USA. FAU - Murthy, Karnam S AU - Murthy KS AD - Virginia Commonwealth University, Richmond, VA, USA. FAU - Bhargava, Valmik AU - Bhargava V AD - Department of Internal Medicine, University of California-San Diego and San Diego VA Healthcare System, San Diego, CA, USA. FAU - Patel, Hemal H AU - Patel HH AD - Department of Anesthesiology, University of California-San Diego and San Diego VA Healthcare System, San Diego, CA, USA.