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Endocrine Abstracts (2017) 49 EP383 | DOI: 10.1530/endoabs.49.EP383

Kyungpook National University Hospital, Dae Gu City, Republic of Korea.


Pathological proliferation and migration of vascular smooth muscle cells (VSMCs) has been implicated in the pathogenesis of accelerated atherosclerosis in patients with diabetes mellitus. Increased aerobic glycolysis is a key feature of cellular phenotypes including cancer and immune cells. However, it remains largely unknown about the role of aerobic glycolysis in atherogenic phenotype of VSMCs. Here, we investigated the role of lactate dehydrogenase-A (LDH-A), which is a key enzyme for glycolysis, on proliferation and migration of VSMCs. Activation of VSMCs with platelet-derived growth factor (PDGF) or fetal bovine serum (FBS) resulted in cellular proliferation and migration and increased glycolytic activity accompanied by the increased expressions of glucose transporter 1 (GLUT1), hexokinase (HK) 2 and LDH-A in primary rat VSMCs. Through wound healing assay, actin stress fiber staining and transwell migration assay, we observed that both pharmacological inhibition (oxamate) and siRNA-mediated knockdown of LDH-A (siLDH-A) effectively inhibited cellular migration. Oxamate reduced PDGF stimulated glucose uptake, lactate production, ATP production and NAD/ nicotinamide adenine dinucleotide (NADH) ratio. Nicotinamide mononucleotide (NMN), nucleotide precursor of NAD+, partially but significantly recovered oxamate treatment or siLDH-A induced inhibition of VSMC proliferation and migration, suggesting NAD+ involvement in LDH-A mediated VSMC proliferation and migration. Taken together, this study shows that enhanced aerobic glycolysis in PDGF- and FBS-stimulated VSMCs plays an important role in their proliferation and migration and suggests that LDHA can be a potential therapeutic target for the prevention of vessel lumen constriction in the course of atherosclerosis or restenosis.

Volume 49

19th European Congress of Endocrinology

Lisbon, Portugal
20 May 2017 - 23 May 2017

European Society of Endocrinology 

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