ArticleAmerican journal of physiology. Heart and circulatory physiology2013
MAP kinase kinase kinase-2 (MEKK2) regulates hypertrophic remodeling of the right ventricle in hypoxia-induced pulmonary hypertension.
Article in American journal of physiology. Heart and circulatory physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 30 citations in OpenAlex.
- Cellular Signalling Networks in High Altitude Pulmonary Hypertension: From Canonical Pathways to Emerging Targets.Cell proliferation · 2026Review
- Functional and molecular determinants of right ventricular response to severe pulmonary hypertension in a large animal model.American journal of physiology. Heart and circulatory physiology · 2023Article
- Hypertrophy of the right ventricle by pulmonary artery banding in rats: a study of structural, functional, and transcriptomics alterations in the right and left ventricles.Frontiers in physiology · 2023Article
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- Nox2 Upregulation and p38α MAPK Activation in Right Ventricular Hypertrophy of Rats Exposed to Long-Term Chronic Intermittent Hypobaric Hypoxia.International journal of molecular sciences · 2020Article
- Oxidative Stress, Kinase Activity and Inflammatory Implications in Right Ventricular Hypertrophy and Heart Failure under Hypobaric Hypoxia.International journal of molecular sciences · 2020Review
- Lung Vascular Remodeling, Cardiac Hypertrophy, and Inflammatory Cytokines in SHIVnef-Infected Macaques.Viral immunology · 2018Article
- Update on novel targets and potential treatment avenues in pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2016Review
- Genetic ablation of interleukin-18 does not attenuate hypobaric hypoxia-induced right ventricular hypertrophy.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- Interaction with the Paxillin LD1 Motif Relieves MEKK2 Auto-inhibition.Journal of molecular signaling · 2015Article
- Effects of Wenyangzhenshuai Granule on ERK1/2 and ERK5 activity in the myocardial tissue in a rabbit model of adriamycin-induced chronic heart failure.International journal of clinical and experimental medicine · 2015Article
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- Supplementing exposure to hypoxia with a copper depleted diet does not exacerbate right ventricular remodeling in mice.PloS one · 2014Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Pulmonary hypertension (PH) results in pressure overload of the right ventricle (RV) of the heart, initiating pathological RV remodeling and ultimately leading to right heart failure. Substantial research indicates that signaling through the MAPK superfamily mediates pathological cardiac remodeling. These considerations led us to test the hypothesis that the regulatory protein MAPKKK-2 (MEKK2) contributes to RV hypertrophy in hypoxia-induced PH. Transgenic mice with global knockout of MEKK2 (MEKK2(-/-) mice) and age-matched wild-type (WT) mice were exposed to chronic hypobaric hypoxia (10% O(2), 6 wk) and compared with animals under normoxia. Exposure to chronic hypoxia induced PH in WT and MEKK2(-/-) mice. In response to PH, WT mice showed RV hypertrophy, demonstrated as increased ratio of RV weight to body weight, increased RV wall thickness at diastole, and increased cardiac myocyte size compared with normoxic control animals. In contrast, each of these measures of RV hypertrophy seen in WT mice after chronic hypoxia was attenuated in MEKK2(-/-) mice. Furthermore, chronic hypoxia elicited altered programs of hypertrophic and inflammatory gene expression consistent with pathological RV remodeling in WT mice; MEKK2 deletion selectively inhibited inflammatory gene expression compared with WT mice. The actions of MEKK2 were mediated in part through regulation of the abundance and phosphorylation of its effector, ERK5. In conclusion, signaling by MEKK2 contributes to RV hypertrophy and altered myocardial inflammatory gene expression in response to hypoxia-induced PH. Therapies targeting MEKK2 may protect the myocardium from hypertrophy and pathological remodeling in human PH.
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