Vardenafil Improves Penile Erection in Type 2 Diabetes Mellitus Patients with Erectile Dysfunction: Role of Tropomyosin

Abstract

Introduction Evidences have been suggested that phosphodiesterase type 5 (PDE5) inhibition promotes vasculoprotective benefits in patients with cardiovascular diseases. Aim The aim of this study is to analyze the systemic effect of PDE5 inhibition in type 2 diabetes mellitus patients with erectile dysfunction (ED) determining changes in the expression levels of plasma proteins. Methods Seventeen patients with controlled type 2 diabetes mellitus and ED were included in the study. Patients received vardenafil hydrochloride 20mg on demand during 12weeks. At the beginning and 12weeks after vardenafil administration, plasma samples were collected and analyzed using proteomics. Main Outcome Measures International Index of Erectile Function-Erectile Function Domain (IIEF-EFD) and plasma protein expression before and after vardenafil administration. Nitrate/nitrite release, PDE5, and soluble guanylate cyclase (sGC) expression and cyclic guanosine monophosphate (cGMP) content in cultured bovine aortic endothelial cells (BAECs). Results The IIEF-EFD score was markedly improved after 12weeks of vardenafil administration. Plasma levels of alpha 1-antitrypsin isotypes 4 and 6 and β-tropomyosin were decreased, whereas apolipoprotein AI isoype 5 was increased 12weeks after vardenafil administration. Only β-tropomyosin plasma levels were inversely correlated with IIEF-EFD score. Tropomyosin has been added to cultured BAECs and after 24hours reduced the protein expression level of sGC-β1 subunit and decreased the cGMP content. Tropomyosin did not modify PDE5 expression and nitric oxide release in BAECs as compared with control BAECs. Vardenafil (10μg/mL) did not modify sGC-β1 subunit expression in tropomyosin+vardenafil-incubated BAECs; however, vardenafil significantly reversed the reduction of cGMP content induced by tropomyosin. Conclusion Vardenafil administration improved erectile functionality in controlled type 2 diabetes mellitus patients with ED, which was associated with reduction of circulating plasma β-tropomyosin levels. Tropomyosin affected by itself the cGMP generating system suggesting a possible new mechanism involved in ED. Vardenafil reversed the reduction effect of cGMP content elicited by tropomyosin in BAECs.

Effect of Pectin on the Expression of Proteins Associated with Mitochondrial Biogenesis and Cell Senescence in HT29-Human Colorectal Adenocarcinoma Cells

“…The gels were blotted onto nitrocellulose (NC) membranes. As previously reported (Zamorano-León et al, 2013; Moñux et al, 2017), NC membranes were blocked with 5% (w/v) bovine serum albumin (BSA) and incubated with monoclonal antibodies against Mfn-1 (1:2,000, sc-166644, Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA), Mfn-2 (1:1,000, sc-2031, Santa Cruz Biotechnology, Inc.), Drp-1 (1:750, Ab56788, Abcam, Cambridge, UK), and B-cell lymphoma 2 (Bcl-2)-antagonist/killer (Bak) (1:1,000, Ab32371, Abcam), and polyclonal antibodies against p53 (1:1,000, sc-6243, Santa Cruz Biotechnology, Inc.), cyclin B1 (1:1,500, Ab2949, Abcam), Bcl-2-associated X protein (Bax) (1:1,000, sc-493, Santa Cruz Biotechnology, Inc.), and Bcl-2 (1:1,000, sc-783, Santa Cruz Biotechnology, Inc.). A monoclonal anti-β-actin antibody (1:7,500, A-5441, Sigma-Aldrich Co.) was used as a control for protein loading.…”

“…Protein expression was determined by Western blotting. In brief, and as we have previously reported (Zamorano-León et al, 2013; Moñux et al, 2017), protein concentrations were estimated using the bicinchoninic acid reagent (Thermo Fisher Scientific, Inc., Waltham, MA, USA), and equal amount (40 μg/lane) of each lysate were loaded onto denaturing sodium dodecyl sulphate-polyacrylamide gel electrophoresis 15% (w/v) polyacrylamide gels. The gels were blotted onto nitrocellulose (NC) membranes.…”

Various interventions for infertility in men with type II diabetes and hypogonadism

“…Administration of testosterone as a replacement therapy has also been shown to improve glycemic control and insulin sensitivity in hypogonadal men with type II diabetes, thus providing additional beneficial metabolic effects (Kapoor, Goodwin et al 2006;Li, Zhao et al 2020). On the other hand, treatment of diabetic hypogonadal men with vardenafil resulted in improved erectile function with no effects on glucose regulation (Goldstein, Young et al 2003;Carson and Lue 2005;Vardi and Nini 2007;Zamorano-Leon, Olivier et al 2013;Santi, Granata et al 2017). Similarly, clomiphene various interventions for infertility in men with type ii diabetes and hypogonadism volume 22, issue 1, january -marCH 2023 citrate, a selective estrogen receptor modulator, has been used for the treatment of male androgen deficiency by raising the endogenous serum FSH, LH and testosterone levels to augment spermatogenesis (Roth, Ryan et al 2013;Wheeler, Sharma et al 2019;Delu, Kiltz et al 2020;Pelusi, Fanelli et al 2021).…”

BRCA2 gene mutations and coagulation-associated biomarkers

“…As we previously reported (11,21,22), each spot intensity volume was processed by background subtraction, and the corresponding spot volume of albumin was used to normalise the total spot volume of each spot. Most of the here analysed spots were identified in previous works published by our laboratory by mass spectrometry using a 4700 Proteomic Analyzer (Applied Biosystem) operated in a reflector positive mode (23,24).…”