Estudios científicos
Resveratrol induces mitochondrial biogenesis in endothelial cells
Abstract:
Pathways that regulate mitochondrial biogenesis are potential therapeutic targets for the amelioration of endothelial dysfunction and vascular disease. Resveratrol was shown to impact mitochondrial function in skeletal muscle and the liver, but its role in mitochondrial biogenesis in endothelial cells remains poorly defined. The present study determined whether resveratrol induces mitochondrial biogenesis in cultured human coronary arterial endothelial cells (CAECs). In CAECs resveratrol increased mitochondrial mass and mitochondrial DNA content, upregulated protein expression of electron transport chain constituents, and induced mitochondrial biogenesis factors (proliferator-activated receptor-coactivator-1alpha, nuclear respiratory factor-1, mitochondrial transcription factor A). Sirtuin 1 (SIRT1) was induced, and endothelial nitric oxide (NO) synthase (eNOS) was upregulated in a SIRT1-dependent manner. Knockdown of SIRT1 (small interfering RNA) or inhibition of NO synthesis prevented resveratrol-induced mitochondrial biogenesis. In aortas of type 2 diabetic (db/db) mice impaired mitochondrial biogenesis was normalized by chronic resveratrol treatment, showing the in vivo relevance of our findings. Resveratrol increases mitochondrial content in endothelial cells via activating SIRT1. We propose that SIRT1, via a pathway that involves the upregulation of eNOS, induces mitochondrial biogenesis. Resveratrol induced mitochondrial biogenesis in the aortas of type 2 diabetic mice, suggesting the potential for new treatment approaches targeting endothelial mitochondria in metabolic diseases.
Comentarios divulgativos:
Las rutas metabólicas que regulan la biogénesis de mitocondrias son potenciales dianas terapeuticas para las disfunciones endoteliales y las enfermedades cardiovasculares. El resveratrol ha mostrado tener impacto en la función mitocondrial en el músculo esquelético y en el hígado, sim embargo su papel en la biogénesis mitocondrial esta pobremente definido. El siguiente estudio determina como el resveratrol induce la biogénesis en cultivos celulares en células endoteliales de lasarterias coronarias (CEAECs). En CEAECs el resveratrol incrementa la masa mitocondrial y el contenido en DNA mitochondrial, aumenta la expresión proteínica y el transporte de electrones e induce la biogénesis de factores mitocondriales.SIRT1 está involucrado en una ruta metabólica que aumenta la actividad de eNOS induciendo la biogénesis mitocondrial. El resveratrol induce la biogénesis mitocondrial en las aortas de ratones que sufren diabetes de tipo II, sugiriendo una diana para tratamientos en enfermedades metabólicas.
