Glutathione S-transferase-micro1 regulates vascular smooth muscle cell proliferation, migration, and oxidative stress.

摘要: Glutathione S-transferase-micro1, GSTM1, belongs to a superfamily of glutathione S-transferases that metabolizes broad range reactive oxygen species and xenobiotics. Across species, genetic variants result in decreased expression the Gstm1 gene are associated with increased susceptibility for vascular diseases, including atherosclerosis humans. We previously identified as positional candidate our mapping study renal injury characterized by medial hypertrophy hyperplasia vessels. To determine role smooth muscle cells (VSMCs), we isolated VSMCs from mouse aortas. demonstrate susceptible C57BL/6 mice have reduced mRNA its protein product compared resistant 129 mice. After serum stimulation, proliferate migrate at much faster rate than VSMCs. Furthermore, higher levels exhibit exaggerated p38 mitogen-activated kinase phosphorylation after exposure H(2)O(2). establish causality, show knockdown small interfering RNA results proliferation dose-dependent manner, well VSMC migration. Moreover, causes attenuates antiproliferative effect Tempol. Our data suggest is novel regulator migration through handling species. Genetic cause decremental change may permit an environment oxidative stress, leading remodeling atherosclerosis.