Role for DNA repair signaling in coronary artery stenosis (1071.9)

Coronary artery stenosis is a vascular disease characterized by sustained inflammation and oxidative stress, leading to DNA damage. Despite these detrimental conditions, coronary artery smooth muscle cells (CoASMC) show increased proliferation and suppressed apoptosis leading to luminal narrowing. PARP-1 is a critical enzyme acting as DNA damage sensor by promoting either DNA repair or apoptosis depending on the amount of damage. Recent studies demonstrated the implication of the glycogen synthase 3 (GSK3) enzyme, which when inhibited, favors DNA repair (promoting cell survival and proliferation) and resistance to apoptosis (by promoting mitochondrial hyperpolarization). Thus, we hypothesized that increased DNA damage in coronary artery of patients with stenosis promotes PARP-1 activation and GSK3 inhibition. In freshly isolated human CoASMC issued from control or stenosed arteries, we measured DNA damage, PARP-1 expression and phosphorylated GSK3 protein levels. We demonstrated that CoASMC from stenosed ...