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Author Kim, Ji-Hyun ♦ Bae, Kwi-Hyun ♦ Byun, Jun-Kyu ♦ Lee, Sungwoo ♦ Kim, Jung-Guk ♦ Lee, In Kyu ♦ Jung, Gwon-Soo ♦ Lee, You Mie
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ARTERIOSCLEROSIS ♦ ATP ♦ CATTLE ♦ CELL PROLIFERATION ♦ GLUCOSE ♦ GLYCOLYSIS ♦ GROWTH FACTORS ♦ HEALING ♦ INHIBITION ♦ LACTATE DEHYDROGENASE ♦ LACTATES ♦ MUSCLES ♦ NEOPLASMS ♦ PATHOGENESIS ♦ RATS ♦ RNA ♦ WOUNDS
Abstract The proliferation and migration of vascular smooth muscle cells (VSMCs) have been implicated in the pathogenesis of atherosclerosis. Increased aerobic glycolysis is a key feature of cellular phenotypes including cancer and immune cells. However, the role of aerobic glycolysis in the atherogenic phenotype of VSMCs remains largely unknown. Here, we investigated the role of lactate dehydrogenase-A (LDHA), which is a key enzyme for glycolysis, in the proliferation and migration of VSMCs. Activation of primary rat VSMCs with fetal bovine serum (FBS) or platelet-derived growth factor (PDGF) increased their proliferation and migration, glycolytic activity, and expression of LDHA. Wound healing and transwell migration assays demonstrated that small interfering RNA-mediated knockdown of LDHA and pharmacological inhibition of LDHA by oxamate both effectively inhibited VSMC proliferation and migration. Inhibition of LDHA activity by oxamate reduced PDGF-stimulated glucose uptake, lactate production, and ATP production. Taken together, this study shows that enhanced glycolysis in PDGF- or FBS-stimulated VSMCs plays an important role in their proliferation and migration and suggests that LDHA is a potential therapeutic target to prevent vessel lumen constriction during the course of atherosclerosis and restenosis. - Highlights: • LDHA levels were upregulated in proliferative and migratory VSMCs. • Inhibition of LDHA suppressed growth factor-stimulated VSMC proliferation/migration. • Inhibition of LDHA reduced growth factor-stimulated glycolysis in VSMCs. • Targeting LDHA has a potential to treat excessive VSMC proliferation and migration.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2017-10-07
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 492
Issue Number 1


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