RT Journal Article
T1 Penile endothelial dysfunction, impaired redox metabolism and blunted mitochondrial bioenergetics in diet-induced obesity: Compensatory role of H2O2
A1 Gomez del Val, Alfonso
A1 Sánchez, Ana
A1 Freire-Agulleiro, Óscar
A1 Martínez, María Pilar
A1 Olmos, Lucia
A1 Sanez Medina, Javier
A1 Comerma-Steffensen, Simon Gabriel
A1 Simonsen, Ulf
A1 Rivera, Luis
A1 López, Miguel
A1 Muñoz Picos, Mercedes
A1 Contreras Jiménez, Cristina
A1 Prieto Ocejo, Dolores
AB ObjectiveErectile dysfunction (ED) is considered an early manifestation of cardiovascular disease (CVD), endothelial dysfunction being the link between CVD and vasculogenic ED. Mitochondrial reactive oxygen species (mtROS) have been involved in the vascular complications of metabolic disorders. The aim of this study was to assess the impact of obesity on endothelial function, redox metabolism and mitochondrial bioenergetics of penile erectile tissue.MethodsWistar rats were fed a high-fat diet (HFD) or standard diet (STD), and penile vascular function was assessed in microvascular myographs. mtROS levels were measured by mitoSOX (O2.-) and Amplex Red (H2O2) fluorimetry, and the effect of the mitochondrial antioxidant mitoTempo on endothelium-dependent relaxations was tested. Mitochondrial respiration of intact microarteries was assessed with an Agilent Seahorse XF Pro analyzer, and the expression of mitochondria redox regulators was analysed by Western blot.ResultsEndothelium-dependent relaxations to acetylcholine (ACh) and to the mitoKATP channel activator BMS191095 were reduced in penile arteries from HFD. mtROS levels were significantly increased and associated with upregulation of the endothelial NADPH oxidase 4 (Nox4) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in HFD erectile tissue. MitoTempo inhibited endothelial relaxations in control and HFD penile arteries. The bioenergetic profile was significantly reduced in HFD penile arteries compared to STD rats.ConclusionsMitochondrial dysfunction with impaired bioenergetics and reduced mitoKATP channel-mediated relaxation underlie endothelial and vascular dysfunction of erectile tissue in obesity, despite a compensatory mechanism that enhances Nox4-derived endothelial vasodilator mtROS. Therapeutic strategies aimed to stabilize mitochondria could restore redox balance and improve mitochondrial bioenergetics thus preventing oxidative stress and vascular dysfunction underlying metabolic disease associated ED.
PB Elsevier
SN 0891-5849
YR 2025
FD 2025
LK https://hdl.handle.net/20.500.14352/125956
UL https://hdl.handle.net/20.500.14352/125956
LA eng
NO Gómez Del Val A, Sánchez A, Freire-Agulleiro Ó, et al. Penile endothelial dysfunction, impaired redox metabolism and blunted mitochondrial bioenergetics in diet-induced obesity: Compensatory role of H2O2. Free Radical Biology and Medicine 2025;230:222–33. https://doi.org/10.1016/j.freeradbiomed.2025.02.004
NO Ministerio de Ciencia, Innovación y Universidades (España)
DS Docta Complutense
RD 30 dic 2025