Oxidative Stress in cardiovascular system

FERRAMOLA MARIANA L; PÉREZ DÍAZ MATÍAS FF; SANTILLÁN LUCAS D; GIMENEZ MARIA SOFIA

Oxidative stress: new research

Nova Publishers

Año: 2011;

Reactive oxygen species (ROS) may directly alter cardiovascular function or cause changes in vascular tone by several mechanisms including altered nitric oxide (NO) bioavailability or signaling. ROS-producing enzymes involved in the increased cardiovascular oxidative stress observed during hypertension include NADPH oxidase (NOX), xanthine oxidase, the mitochondrial respiratory chain and the uncoupled endothelial NO synthase. An increasing body of evidence suggests that oxidative stress, which results in an excessive generation of ROS, has a key role in the pathogenesis of cardiovascular diseases. ROS regulate vascular function by modulating cell growth, apoptosis/anoikis, migration, inflammation, secretion, and extracellular matrix protein production. Oxidative stress and associated oxidative damage are mediators of vascular injury and inflammation in many cardiovascular diseases, including hypertension, hyperlipidemia, and diabetes. Anti-oxidants and agents that interrupt NAD(P)H oxidase-driven superoxide anion (O2•-) production regress vascular remodeling, improve endothelial function, reduce inflammation, and decrease blood pressure in hypertensive models. The NOX2-containing reduced nicotinamide-adenine dinucleotide phosphate oxidase contributes significantly to the processes underlying adverse cardiac remodeling and contractile dysfunction post- myocardial infarct. Large increases in ROS are associated with damage to mitochondria, DNA, proteins and lipids. In the heart this ultimately leads to apoptosis and loss of myocytes. However sub- lethal increases in ROS can activate hypertrophic signaling kinases and transcription factors including, CaMK and serine-threonine and tyrosine kinases. Calcium is also an important signaling molecule and a mediator of hypertrophic signaling pathways. ROS and calcium seem to participate as partners in pathological cardiac remodelling but their interaction and early mechanisms associated with the development of cardiac hypertrophy are poorly understood. An increase in cytoplasmic calcium can potentiate cellular oxidative stress via effects on mitochondrial metabolism. In addition oxidative stress can regulate the function of calcium channels and transporters. FoxO transcription factors are critical mediators of oxidative stress resistance in multiple cell types, but cardioprotective function is not well understood. FoxOs participate in cardiomyocyte survival during conditions of oxidative stress through induction of antioxidants and cell survival pathways. Silent information regulator 1 (Sirt1), a class III histone deacetylase and a member of the sirtuin family, inhibits cell death in cardiomyocytes in response to stress and retards aging in the heart. Sirt1 protects the heart from ischemia/reperfusion injury through upregulation of antioxidants and downregulation of proapoptotic molecules via activation of FoxO transcription factors and decreases in oxidative stress. The transcription factor Nrf2 regulates the expression of important cytoprotective-antioxidant enzymes. Heat shock transcription factor-1 inhibits H2O2-induced apoptosis via down-regulation of reactive oxygen species in cardiac myocytes. Angiotensin II inactivates FOXO3a by activating Akt, leading to a reduction in the expression of the antioxidant Mn-SOD, and thereby potentially contributing to oxidative stress in the myocardium. On the other hand, it is known that obesogenic high fat western diet induces oxidative stress and apoptosis in rat heart. In this chapter, we will discuss the most recent articles concerning the effect of oxidative stress on cardiovascular system and the mechanism of action in each case, showing the transcription factors involved at each point.