01 March 2017 by Rajamma Mathew

Caveolin-1 loss/dysfunction may in part facilitate metabolic shift in pulmonary hypertension

We have previously reported progressive loss of endothelial caveolin-1 (cav-1) and enhanced cav-1 expression in smooth muscle cells (SMC) in pulmonary hypertension (PH). Accelerating the PH progression by exposing monocrotaline (M)-treated rats to hypoxia,  extensive endothelial damage, enhanced cav-1 expression in SMC and neointima formation are observed by 4 weeks.  Neointimal cells have normal eNOS and scant cav-1 expression; a set-up for oxidative and nitrosative stress. Cav-1 has been shown to regulate cell proliferation, oxidative stress and metabolic shift. Recent studies indicate that the metabolic shift is an important aspect of PH. We hypothesized that cav-1 loss/dysfunction may have a role in the metabolic shift observed in PH. To test our hypothesis, we examined rats treated with M, and M + hypobaric hypoxia (M+H) and compared with the controls (C). At 4 weeks, M+H gr. revealed significant PH compared with M gr. Cav-1 expression was significantly reduced in M gr; but closer to normal in the M+H gr.  The expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), MnSOD and Glut 1 was significantly increased in the M+H gr. Interestingly, in cancer, loss of cav-1 function leads to oxidative stress resulting in the activation of Nrf2 and translocation to nucleus where it activates MnSOD, leading to p53 inhibition and aerobic glycolysis, thus facilitating the survival of proliferating cells. In contrast, cav-1 links free radical pathways to the activation of p53, thus maintains anti-proliferative and apoptotic state.  Furthermore, loss of cav-1 function results in increased Glut1 expression which can increase glucose uptake and facilitate aerobic glycolysis. Our preliminary data suggest that cav-1 loss/dysfunction may facilitate metabolic shift in PH.  

Key Contributors

Rajamma Mathew, Jing Huang, Michael H Gewitz Section of Pediatric Cardiology, New York Medical College, Valhalla, NY 10595


Comments (0)

Our research platform is the world.

Through worldwide collaboration, we can begin to answer the question of a global disease.

Join the PVRI
standard-example-image.jpg