Nox2 Upregulation and p38 alpha MAPK Activation in Right Ventricular Hypertrophy of Rats Exposed to Long-Term Chronic Intermittent Hypobaric Hypoxia

Pena, Eduardo; Siques, Patricia; Brito, Julio; Arribas, Silvia M.; Boeger, Rainer; Hannemann, Juliane; Leon-Velarde, Fabiola; Carmen Gonzalez, M.; Rosario Lopez, M.; Lopez de Pablo, Angel Luis

Abstract

One of the consequences of high altitude (hypobaric hypoxia) exposure is the development of right ventricular hypertrophy (RVH). One particular type of exposure is long-term chronic intermittent hypobaric hypoxia (CIH); the molecular alterations in RVH in this particular condition are less known. Studies show an important role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex-induced oxidative stress and protein kinase activation in different models of cardiac hypertrophy. The aim was to determine the oxidative level, NADPH oxidase expression and MAPK activation in rats with RVH induced by CIH. Male Wistar rats were randomly subjected to CIH (2 days hypoxia/2 days normoxia; n = 10) and normoxia (NX; n = 10) for 30 days. Hypoxia was simulated with a hypobaric chamber. Measurements in the RV included the following: hypertrophy, Nox2, Nox4, p22phox, LOX-1 and HIF-1 alpha expression, lipid peroxidation and H2O2 concentration, and p38 alpha and Akt activation. All CIH rats developed RVH and showed an upregulation of LOX-1, Nox2 and p22phox and an increase in lipid peroxidation, HIF-1 alpha stabilization and p38 alpha activation. Rats with long-term CIH-induced RVH clearly showed Nox2, p22phox and LOX-1 upregulation and increased lipid peroxidation, HIF-1 alpha stabilization and p38 alpha activation. Therefore, these molecules may be considered new targets in CIH-induced RVH.

Más información

Título según WOS: Nox2 Upregulation and p38 alpha MAPK Activation in Right Ventricular Hypertrophy of Rats Exposed to Long-Term Chronic Intermittent Hypobaric Hypoxia
Título de la Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volumen: 21
Número: 22
Editorial: MDPI
Fecha de publicación: 2020
DOI:

10.3390/ijms21228576

Notas: ISI