Role of c-Src and reactive oxygen species in cardiovascular diseases

Oxidative stress, caused by the over production of oxidants or inactivity of antioxidants, can modulate the redox state of several target proteins such as tyrosine kinases, mitogen-activated protein kinases and tyrosine phosphatases. c-Src is one such non-receptor tyrosine kinase which activates NADPH oxidases (Noxs) in response to various growth factors and shear stress. Interaction between c-Src and Noxs is influenced by cell type and primary messengers such as angiotensin II, which binds to G-protein coupled receptor and activates the intracellular signaling cascade. c-Src stimulated activation of Noxs results in elevated release of intracellular and extracellular reactive oxygen species (ROS). These ROS species disturb vascular homeostasis and cause cardiac hypertrophy, coronary artery disease, atherosclerosis and hypertension. Interaction between c-Src and ROS in the pathobiology of cardiac fibrosis is hypothesized to be influenced by cell type and stimuli. c-Src and ROS have a bidirectional relationship, thus increased ROS levels due to c-Src mediated activation of Noxs can further activate c-Src by promoting the oxidation and sulfenylation of critical cysteine residues. This review highlights the role of c-Src and ROS in mediating downstream signaling pathways underlying cardiovascular diseases. Furthermore, due to the central role of c-Src in activation of various signaling proteins involved in differentiation, migration, proliferation, and cytoskeletal reorganization of vascular cells, it is presented as therapeutic target for treating cardiovascular diseases except cardiac fibrosis.

Automated summary

Oxidative stress affects the redox state of various target proteins, including tyrosine kinases, mitogen-activated protein kinases, and tyrosine phosphatases. c-Src is a non-receptor tyrosine kinase that can activate NADPH oxidases in response to different stimuli. The interaction between c-Src and Noxs is influenced by cell type and primary messengers. Additionally, c-Src and ROS have a bidirectional relationship in the pathobiology of cardiac fibrosis.