RESUMEN
The generation of reactive oxygen species (ROS) is a fundamental aspect of normal human biology. However, when ROS generation exceeds endogenous antioxidant capacity, oxidative stress arises. If unchecked, ROS production and oxidative stress mediate tissue and cell damage that can spiral in a cycle of inflammation and more oxidative stress. This article is part 1 of a 3-part series covering the role of oxidative stress in cardiovascular disease. The broad theme of this first paper is the mechanisms and biology of oxidative stress. Specifically, the authors review the basic biology of oxidative stress, relevant aspects of mitochondrial function, and stress-related cell death pathways (apoptosis and necrosis) as they relate to the heart and cardiovascular system. They then explore telomere biology and cell senescence. As important regulators and sensors of oxidative stress, telomeres are segments of repetitive nucleotide sequence at each end of a chromosome that protect the chromosome ends from deterioration.
Asunto(s)
Envejecimiento , Enfermedades Cardiovasculares/metabolismo , Estrés Oxidativo , Animales , Apoptosis , Humanos , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Subendothelial mast cells have been implicated in the pathogenesis of allergic inflammation, in atherosclerosis, and in the regulation of vascular tone. Because endothelin-1 (ET-1) is an important regulator of vascular tone and has also been implicated in the pathogenesis of atherosclerosis, we studied the role of mast cells in the metabolism of endothelial cell-derived ET-1. In mast cell-endothelial cell cocultures, activation of the mast cells with ensuing degranulation was accompanied by the increased expression of ET-1 mRNA in the endothelial cells, yet the immunoreactive ET-1 protein in the coculture medium disappeared almost completely during the 24-hour coculture. Activation of the mast cells with the ensuing degranulation resulted in proteolytic degradation of ET-1 by the 2 neutral proteases, chymase and carboxypeptidase A, of the exocytosed mast cell granules. With synthetic ET-1 and purified mast cell granule enzymes, efficient degradation of ET-1 by chymase and carboxypeptidase A was verified. These in vitro results imply a novel role for mast cell-derived neutral proteases in ET-1 metabolism and suggest that activated subendothelial mast cells are important local regulators of ET-1 metabolism.