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BMPR2 preserves mitochondrial function and DNA during reoxygenation to promote endothelial cell survival and reverse pulmonary hypertension

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BMPR2 preserves mitochondrial function and DNA during reoxygenation to promote endothelial cell survival and reverse pulmonary hypertension. / Diebold, Isabel; Hennigs, Jan K; Miyagawa, Kazuya; Li, Caiyun G; Nickel, Nils P; Kaschwich, Mark; Cao, Aiqin; Wang, Lingli; Reddy, Sushma; Chen, Pin-I; Nakahira, Kiichi; Alcazar, Miguel A Alejandre; Hopper, Rachel K; Ji, Lijuan; Feldman, Brian J; Rabinovitch, Marlene.

In: CELL METAB, Vol. 21, No. 4, 07.04.2015, p. 596-608.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Diebold, I, Hennigs, JK, Miyagawa, K, Li, CG, Nickel, NP, Kaschwich, M, Cao, A, Wang, L, Reddy, S, Chen, P-I, Nakahira, K, Alcazar, MAA, Hopper, RK, Ji, L, Feldman, BJ & Rabinovitch, M 2015, 'BMPR2 preserves mitochondrial function and DNA during reoxygenation to promote endothelial cell survival and reverse pulmonary hypertension', CELL METAB, vol. 21, no. 4, pp. 596-608. https://doi.org/10.1016/j.cmet.2015.03.010

APA

Diebold, I., Hennigs, J. K., Miyagawa, K., Li, C. G., Nickel, N. P., Kaschwich, M., Cao, A., Wang, L., Reddy, S., Chen, P-I., Nakahira, K., Alcazar, M. A. A., Hopper, R. K., Ji, L., Feldman, B. J., & Rabinovitch, M. (2015). BMPR2 preserves mitochondrial function and DNA during reoxygenation to promote endothelial cell survival and reverse pulmonary hypertension. CELL METAB, 21(4), 596-608. https://doi.org/10.1016/j.cmet.2015.03.010

Vancouver

Diebold I, Hennigs JK, Miyagawa K, Li CG, Nickel NP, Kaschwich M et al. BMPR2 preserves mitochondrial function and DNA during reoxygenation to promote endothelial cell survival and reverse pulmonary hypertension. CELL METAB. 2015 Apr 7;21(4):596-608. https://doi.org/10.1016/j.cmet.2015.03.010

Bibtex

@article{99f1276e96e1438bbfe104103243ef66,
title = "BMPR2 preserves mitochondrial function and DNA during reoxygenation to promote endothelial cell survival and reverse pulmonary hypertension",
abstract = "Mitochondrial dysfunction, inflammation, and mutant bone morphogenetic protein receptor 2 (BMPR2) are associated with pulmonary arterial hypertension (PAH), an incurable disease characterized by pulmonary arterial (PA) endothelial cell (EC) apoptosis, decreased microvessels, and occlusive vascular remodeling. We hypothesized that reduced BMPR2 induces PAEC mitochondrial dysfunction, promoting a pro-inflammatory or pro-apoptotic state. Mice with EC deletion of BMPR2 develop hypoxia-induced pulmonary hypertension that, in contrast to non-transgenic littermates, does not reverse upon reoxygenation and is associated with reduced PA microvessels and lung EC p53, PGC1α and TFAM, regulators of mitochondrial biogenesis, and mitochondrial DNA. Decreasing PAEC BMPR2 by siRNA during reoxygenation represses p53, PGC1α, NRF2, TFAM, mitochondrial membrane potential, and ATP and induces mitochondrial DNA deletion and apoptosis. Reducing PAEC BMPR2 in normoxia increases p53, PGC1α, TFAM, mitochondrial membrane potential, ATP production, and glycolysis, and induces mitochondrial fission and a pro-inflammatory state. These features are recapitulated in PAECs from PAH patients with mutant BMPR2.",
author = "Isabel Diebold and Hennigs, {Jan K} and Kazuya Miyagawa and Li, {Caiyun G} and Nickel, {Nils P} and Mark Kaschwich and Aiqin Cao and Lingli Wang and Sushma Reddy and Pin-I Chen and Kiichi Nakahira and Alcazar, {Miguel A Alejandre} and Hopper, {Rachel K} and Lijuan Ji and Feldman, {Brian J} and Marlene Rabinovitch",
note = "Copyright {\textcopyright} 2015 Elsevier Inc. All rights reserved.",
year = "2015",
month = apr,
day = "7",
doi = "10.1016/j.cmet.2015.03.010",
language = "English",
volume = "21",
pages = "596--608",
journal = "CELL METAB",
issn = "1550-4131",
publisher = "Cell Press",
number = "4",

}

RIS

TY - JOUR

T1 - BMPR2 preserves mitochondrial function and DNA during reoxygenation to promote endothelial cell survival and reverse pulmonary hypertension

AU - Diebold, Isabel

AU - Hennigs, Jan K

AU - Miyagawa, Kazuya

AU - Li, Caiyun G

AU - Nickel, Nils P

AU - Kaschwich, Mark

AU - Cao, Aiqin

AU - Wang, Lingli

AU - Reddy, Sushma

AU - Chen, Pin-I

AU - Nakahira, Kiichi

AU - Alcazar, Miguel A Alejandre

AU - Hopper, Rachel K

AU - Ji, Lijuan

AU - Feldman, Brian J

AU - Rabinovitch, Marlene

N1 - Copyright © 2015 Elsevier Inc. All rights reserved.

PY - 2015/4/7

Y1 - 2015/4/7

N2 - Mitochondrial dysfunction, inflammation, and mutant bone morphogenetic protein receptor 2 (BMPR2) are associated with pulmonary arterial hypertension (PAH), an incurable disease characterized by pulmonary arterial (PA) endothelial cell (EC) apoptosis, decreased microvessels, and occlusive vascular remodeling. We hypothesized that reduced BMPR2 induces PAEC mitochondrial dysfunction, promoting a pro-inflammatory or pro-apoptotic state. Mice with EC deletion of BMPR2 develop hypoxia-induced pulmonary hypertension that, in contrast to non-transgenic littermates, does not reverse upon reoxygenation and is associated with reduced PA microvessels and lung EC p53, PGC1α and TFAM, regulators of mitochondrial biogenesis, and mitochondrial DNA. Decreasing PAEC BMPR2 by siRNA during reoxygenation represses p53, PGC1α, NRF2, TFAM, mitochondrial membrane potential, and ATP and induces mitochondrial DNA deletion and apoptosis. Reducing PAEC BMPR2 in normoxia increases p53, PGC1α, TFAM, mitochondrial membrane potential, ATP production, and glycolysis, and induces mitochondrial fission and a pro-inflammatory state. These features are recapitulated in PAECs from PAH patients with mutant BMPR2.

AB - Mitochondrial dysfunction, inflammation, and mutant bone morphogenetic protein receptor 2 (BMPR2) are associated with pulmonary arterial hypertension (PAH), an incurable disease characterized by pulmonary arterial (PA) endothelial cell (EC) apoptosis, decreased microvessels, and occlusive vascular remodeling. We hypothesized that reduced BMPR2 induces PAEC mitochondrial dysfunction, promoting a pro-inflammatory or pro-apoptotic state. Mice with EC deletion of BMPR2 develop hypoxia-induced pulmonary hypertension that, in contrast to non-transgenic littermates, does not reverse upon reoxygenation and is associated with reduced PA microvessels and lung EC p53, PGC1α and TFAM, regulators of mitochondrial biogenesis, and mitochondrial DNA. Decreasing PAEC BMPR2 by siRNA during reoxygenation represses p53, PGC1α, NRF2, TFAM, mitochondrial membrane potential, and ATP and induces mitochondrial DNA deletion and apoptosis. Reducing PAEC BMPR2 in normoxia increases p53, PGC1α, TFAM, mitochondrial membrane potential, ATP production, and glycolysis, and induces mitochondrial fission and a pro-inflammatory state. These features are recapitulated in PAECs from PAH patients with mutant BMPR2.

U2 - 10.1016/j.cmet.2015.03.010

DO - 10.1016/j.cmet.2015.03.010

M3 - SCORING: Journal article

C2 - 25863249

VL - 21

SP - 596

EP - 608

JO - CELL METAB

JF - CELL METAB

SN - 1550-4131

IS - 4

ER -