Effect of Angioplasty and Hypoxia on Mitochondrial Biogenesis and Intimal Hyperplasia in Swine Coronary Artery

Abstract

Intimal hyperplasia (IH) is a complication of coronary intervention. Intimal injury happens after balloon angioplasty. This leads to neo-intimal formation which increases in thickness. This leads to further complications of restenosis, atherosclerosis and thrombosis. The thick intimal layer creates regions of hypoxia in the layers of the vessel. The aim of the study was to investigate the mitochondrial function in the IH. Expression of mitochondrial markers in the vascular smooth muscle cells (VSMC) in hypoxic and pro-inflammatory environment are studied.|The results show that there is a significant decrease in the expression of mitochondrial biogenesis marker, PGC-1a in swine with IH (p=0.006: 95%CI: -48.8 to -27.4). PGC-1a expression was also decreased under influence of hypoxia to VSMCs (p=0.03, 95%CI: 4.6 to 110.3). The study found no significant change in expression of mitochondrial markers PGC- 1a, citrate synthase, complex-1 under pro-inflammatory cytokines IL-6 and TNF-a (IL6: PGC-1a p=0.98: CS p=0.25: Complex-1 p=0.08) (TNF-a: PGC-1a p=0.30: CS p=0.72: Complex-1 p=0.08). Hypoxia significantly elevated reactive oxygen species (ROS) levels expression (p=0.0001, 95% CI: -157.48 to -136.9). ROS expression did not show any significance under IL-6 and TNF-a treatment of VSMCs (IL-6 p=0.20 95%CI: -1.5 to 7.1) (TNF-a: p=0.53, 95%CI: -9.9 to 5.1). Hypoxia and pro-inflammatory cytokines IL-6, TNF-a did not show any significant change in proliferation of VSMCs which was measured using BrdU (5 Bromo-2-deoxy-uridine) assay (hypoxia p=0.72: IL-6 p=0.09: TNF-a p=0.25). These findings demonstrate that there could be an association between decreased expression of mitochondrial biogenesis marker PGC-1a with IH. Hypoxia induced decrease in PGC-1a expression and increased ROS expression could be associated with IH in coronary artery.