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Advances in Glycolysis Metabolism of Atherosclerosis

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Abstract

Glycolysis is an important way for various cells such as vascular wall endothelial cells, smooth muscle cells, macrophages, and other cells to obtain energy. In pathological conditions, it can participate in the process of AS by regulating lipid deposition, calcification, angiogenesis in plaques, etc., together with its metabolite lactic acid. Recent studies have shown that lactate-related lactylation modifications are ubiquitous in the human proteome and are involved in the regulation of various inflammatory diseases. Combined with the distribution and metabolic characteristics of cells in the plaque in the process of AS, glycolysis-lactate-lactylation modification may be a new entry point for targeted intervention in atherosclerosis in the future. Therefore, this article intends to elaborate on the role and mechanism of glycolysis-lactate-lactylation modification in AS, as well as the opportunities and challenges in targeted therapy, hoping to bring some help to relevant scholars in this field.

Graphical Abstract

In atherosclerosis, glycolysis, lactate, and lactylation modification as a metabolic sequence affect the functions of macrophages, smooth muscle cells, endothelial cells, lymphocytes, and other cells and interfere with processes such as vascular calcification and intraplaque neovascularization to influence the progression of atherosclerosis.

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Abbreviations

AS:

Atherosclerosis

ABCA1:

ATP-binding cassette transporter A1

ECs:

Endothelial cells

ECM:

Extracellular matrix

HK2:

Hexokinase 2

HIF-1α:

Hypoxia-inducible factor-1α

HDL:

High-density lipoprotein

IL-6:

Interleukin-6

IL-17:

Interleukin-17

IL-1β:

Interleukin-1β

GPR81:

G protein-coupled receptor 81

LDHA:

Lactate dehydrogenase A

MCA:

Metabolic control analysis

MCT:

Monocarboxylate transporter

NDRG:

N-Myc downstream-regulated gene

NF-κB:

Nuclear factor-kappa B

OSS:

Oscillatory shear stress

oxLDL:

Oxidized low-density lipoprotein

PKM2:

Pyruvate kinase isozyme typeM2

PDGF:

Platelet-derived growth factor

PFK-1:

Phosphofructokinase 1

PDH:

Pyruvate dehydrogenase

PKB/Akt:

Protein kinase B

PRKA/AMPK:

Protein kinase AMP-activated; AMP-activated protein kinases

STAT3:

Signal transducer and activator of transcription 3

TLR:

Toll-like receptor

TNF-α:

Tumor necrosis factor-α

VSMCs:

Vascular smooth muscle cells

VCAM-1:

Vascular cell adhesion molecule-1

VEGF:

Vascular endothelial growth factor

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Funding

This work was supported by grants from the National Natural Science Foundation of China (82070455), the related Foundation of Jiangsu Province (BK20201225), and the Medical Innovation Team Project of Jiangsu Province (CXTDA2017010).

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  1. Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, China

    Ruhan Xu, Wei Yuan & Zhongqun Wang

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Xu, R., Yuan, W. & Wang, Z. Advances in Glycolysis Metabolism of Atherosclerosis. J. of Cardiovasc. Trans. Res. 16, 476–490 (2023). https://doi.org/10.1007/s12265-022-10311-3

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