What question did this study set out to answer?

To elucidate how hypoxia-induced mitochondrial reactive oxygen species and subsequent glycolytic shifts drive pulmonary artery smooth muscle cell proliferation and vascular remodeling in pulmonary hypertension.

December 1, 2022Journal of Molecular Cell BiologyOpen Access

Histone lactylation driven by mROS-mediated glycolytic shift promotes hypoxic pulmonary hypertension

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Authors

JCJian Chen MZMeiling Zhang YLYanjie Liu

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Overview

Preclinical study demonstrates that mROS-driven histone lactylation promotes pulmonary vascular remodeling in hypoxic rat models, highlighting lactate manipulation as a therapeutic strategy.

Key Points

To elucidate how hypoxia-induced mitochondrial reactive oxygen species and subsequent glycolytic shifts drive pulmonary artery smooth muscle cell proliferation and vascular remodeling in pulmonary hypertension.
Investigated hypoxia-induced metabolic signaling pathways in pulmonary artery smooth muscle cells (PASMCs) using H3K18la and HIF-1α ChIP-seq analyses.
Assessed genetic knockdown of Pdk1 and Pdk2 along with pharmacological lactate dehydrogenase inhibition in cell culture and hypoxic pulmonary hypertension rat models.
Hypoxia-induced mROS inhibited HIF-1α hydroxylation to activate the HIF-1α/PDK1&PDK2/p-PDH-E1α axis, triggering lactate accumulation and H3K18la histone lactylation at growth-related target genes including Bmp5, Trpc5, and Kit.
Knockdown of Pdk1 and Pdk2 or pharmacological inhibition of lactate dehydrogenase diminished histone lactylation, attenuated PASMC proliferation, and ameliorated vascular remodeling in hypoxic pulmonary hypertension rats.

Cite This Study

Chen et al. (2022) studied this question.

synapsesocial.com/papers/69dd4b8d0a7b4bc8c41012fb https://doi.org/10.1093/jmcb/mjac073

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December 1, 2022Journal of Molecular Cell BiologyOpen Access

Histone lactylation driven by mROS-mediated glycolytic shift promotes hypoxic pulmonary hypertension

View Full Paper

Ask AI

Bookmark

Authors

JCJian Chen MZMeiling Zhang YLYanjie Liu

Discussion

Member takes

Overview

Preclinical study demonstrates that mROS-driven histone lactylation promotes pulmonary vascular remodeling in hypoxic rat models, highlighting lactate manipulation as a therapeutic strategy.

Key Points

To elucidate how hypoxia-induced mitochondrial reactive oxygen species and subsequent glycolytic shifts drive pulmonary artery smooth muscle cell proliferation and vascular remodeling in pulmonary hypertension.
Investigated hypoxia-induced metabolic signaling pathways in pulmonary artery smooth muscle cells (PASMCs) using H3K18la and HIF-1α ChIP-seq analyses.
Assessed genetic knockdown of Pdk1 and Pdk2 along with pharmacological lactate dehydrogenase inhibition in cell culture and hypoxic pulmonary hypertension rat models.
Hypoxia-induced mROS inhibited HIF-1α hydroxylation to activate the HIF-1α/PDK1&PDK2/p-PDH-E1α axis, triggering lactate accumulation and H3K18la histone lactylation at growth-related target genes including Bmp5, Trpc5, and Kit.
Knockdown of Pdk1 and Pdk2 or pharmacological inhibition of lactate dehydrogenase diminished histone lactylation, attenuated PASMC proliferation, and ameliorated vascular remodeling in hypoxic pulmonary hypertension rats.

Cite This Study

Chen et al. (2022) studied this question.

synapsesocial.com/papers/69dd4b8d0a7b4bc8c41012fb https://doi.org/10.1093/jmcb/mjac073

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