04 February 2019 by Rajamma Mathew

NRH: Quinone Reductase 2 (NQO2), a New Player in Pulmonary Hypertension?

We have previously shown endothelial disruption and progressive loss of endothelial caveolin-1
(cav-1), followed by enhanced expression of cav-1 in smooth muscle cells (SMC) in the
monocrotaline (MCT) model of pulmonary hypertension (PH). This cav-1 in SMC exhibits proproliferative
and possibly pro-migratory activities; therefore, it is of interest to identify and
characterize endogenous proteins that might regulate and counter the effects of cav-1. NQO2,
a phase II detoxifying enzyme, activated in Nrf2-dependent and independent manner, has been
shown to have dual function; antioxidant, anti-proliferative and pro-proliferative. Interestingly, in
a carotid artery injury model, silencing NQO2 has been shown to inhibit neointima formation.
We have recently shown that NQO2 has a cav-1 binding site, and is partially localized at the cell
membrane site, thus, potentially available for protein-protein interaction. We have further shown
that both cav-1 and NQO2 carried by large extracellular vesicles participate in prostate cancer
metastasis. In view of these findings, we examined the hemodynamic data, expression of cav-1,
Nrf2 and NQO2 in rat lungs 4 weeks after treatment with MCT (M), hypobaric hypoxia (H) and in
MCT-treated rats exposed to hypoxia (M+H), and compared with the controls (C). M, H and
M+H groups showed significant PH and RVH. Cav-1 expression was significantly reduced in M
(16% of C) and in M+H it was 82% of C, concomitant with the enhanced expression of cav-1 in
SMC. No change in cav-1 was observed in H. Significantly increased Nrf2 was observed only in
M+H. NQO2 expression was significant increased in the M and M+H, but not in the H. In
conclusion, loss of endothelial cav-1 correlates with increased NQO2 expression. The enhanced
expression of cav-1 in SMC and NQO2 may in part be responsible for cell proliferation and
migration in PH.
Supported in part by CMREF (RM)

Key Contributors

Rajamma Mathew1,2, Jing Huang 2, Tze-Chen Hsieh3, Thambi Dorai 3,4, Joseph M Wu3 Departments of 1. Pediatrics, 2. Physiology, 3. Biochemistry and Molecular Biology, and 4. Urology, New York Medical College, Valhalla, NY 10595

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