Altered Penile Caveolin Expression in Diabetes: Potential Role in Erectile Dysfunction
| Autor: | Valmik Bhargava, Jay Parikh, Dimosthenis Giamouridis, Adam Kassan, Johnny Fu, Alice E. Zemljic-Harpf, M. Raj Rajasekaran, Tung-Chin Hsieh, Hemal H. Patel, Karnam S. Murthy |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Endocrinology Diabetes and Metabolism Caveolin 1 030232 urology & nephrology Hemodynamics Erectile tissue Cardiovascular Medical and Health Sciences chemistry.chemical_compound Mice 0302 clinical medicine Endocrinology Caveolin-1 Erectile Dysfunction Caveolin 2.1 Biological and endogenous factors Aetiology Cyclic GMP Mice Knockout Penile Erection Diabetes High-Fat Diet Type 2 Diabetes Psychiatry and Mental health medicine.anatomical_structure cGMP-specific phosphodiesterase type 5 cardiovascular system Perfusion Type 2 medicine.drug Urologic Diseases medicine.medical_specialty Nitric Oxide Synthase Type III Knockout Urology Biology Article 03 medical and health sciences Vascular Internal medicine Diabetes Mellitus medicine Animals Endothelium Obstetrics & Reproductive Medicine Cyclic guanosine monophosphate Prevention Contraception/Reproduction Microcirculation Psychology and Cognitive Sciences Streptozotocin medicine.disease 030104 developmental biology Erectile dysfunction Reproductive Medicine chemistry Diabetes Mellitus Type 2 Endothelium Vascular Penis |
| Zdroj: | The journal of sexual medicine, vol 14, iss 10 |
| Popis: | 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 [3H] 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 E1 (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 E1 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|