Study of molecular mechanisms that mediate the actions of the NADPH oxidase present in the arterial wall in hypertension

REDONDO ANALIA

Buenos Aires

Simposio; Fronteras en BioCiencias; 2012

Sociedad Max Planck y el Ministerio de Ciencia, Tecnología e Innovación Productiva

All types of vascular cells produce reactive oxygen species (ROS), mainly through the membrane-associated NADPH oxidases systems. The vascular NADPH oxidases have been found to be essential in the physiological response of vascular cells, including growth, migration, and modification of the extracellular matrix. Oxidative stress is a mediator of vascular injury and inflammation in many cardiovascular diseases.  Angiotensin II (AII) is an important vasoconstrictor and also regulates many processes involved in vascular pathophysiology, including cell growth, apoptosis, migration, inflammatory response and remodeling of the extracellular matrix. Furthermore, AII stimulates the production of ROS through NADPH oxidase activation. The aim of this project is to investigate the role of NADPH oxidase enzyme complex in adventitial fibroblasts and vascular smooth muscle cells (VSMCs) of animals with essential hypertension. We studied the behavior of VSMCs stimulated with AII and we found a significantly increased in ROS production via activation of NADPH oxidase complex. This effect is reversed in the presence of Apocynin, a selective NADPH oxidase inhibitor. We also found that AII induced cell growth and cell migration and increased ERK phosphorylation Our perspectives are to characterize and to evaluate the expression of the different subunits of NADPH oxidase complex in the vascular wall from different animal models (WKY and SHR), and to study the effect of AII on ROS production, NADPH oxidase activation and redox-dependent behavior of fibroblasts obtained from the vascular adventitia.