Aldehyde dehydrogenase 2 protects against oxidative stress associated with pulmonary arterial hypertension.
In: Redox biology, Jg. 11 (2017-04-01), S. 286
Online
academicJournal
Zugriff:
The cardioprotective benefits of aldehyde dehydrogenase 2 (ALDH2) are well established, although the regulatory role of ALDH2 in vascular remodeling in pulmonary arterial hypertension (PAH) is largely unknown. ALDH2 potently regulates the metabolism of aldehydes such as 4-hydroxynonenal (4-HNE), the endogenous product of lipid peroxidation. Thus, we hypothesized that ALDH2 ameliorates the proliferation and migration of human pulmonary artery smooth muscle cells (HPASMCs) by inhibiting 4-HNE accumulation and regulating downstream signaling pathways, thereby ameliorating pulmonary vascular remodeling. We found that low concentrations of 4-HNE (0.1 and 1μM) stimulated cell proliferation by enhancing cyclin D1 and c-Myc expression in primary HPASMCs. Low 4-HNE concentrations also enhanced cell migration by activating the nuclear factor kappa B (NF-κB) signaling pathway, thereby regulating matrix metalloprotein (MMP)-9 and MMP2 expression in vitro. In vivo, Alda-1, an ALDH2 agonist, significantly stimulated ALDH2 activity, reducing elevated 4-HNE and malondialdehyde levels and right ventricular systolic pressure in a monocrotaline-induced PAH animal model to the level of control animals. Our findings indicate that 4-HNE plays an important role in the abnormal proliferation and migration of HPASMCs, and that ALDH2 activation can attenuate 4-HNE-induced PASMC proliferation and migration, possibly by regulating NF-κB activation, in turn ameliorating vascular remodeling in PAH. This mechanism might reflect a new molecular target for treating PAH.
(Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)
Titel: |
Aldehyde dehydrogenase 2 protects against oxidative stress associated with pulmonary arterial hypertension.
|
---|---|
Autor/in / Beteiligte Person: | Xu, T ; Liu, S ; Ma, T ; Jia, Z ; Zhang, Z ; Wang, A |
Link: | |
Zeitschrift: | Redox biology, Jg. 11 (2017-04-01), S. 286 |
Veröffentlichung: | [Amsterdam]: Elsevier, B.V., [2013]-, 2017 |
Medientyp: | academicJournal |
ISSN: | 2213-2317 (electronic) |
DOI: | 10.1016/j.redox.2016.12.019 |
Schlagwort: |
|
Sonstiges: |
|