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Critical regulation of atherosclerosis by the KCa3.1 channel and the retargeting of this therapeutic target in in-stent neoatherosclerosis

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Abstract

Coronary heart disease is a serious cardiovascular illness. Percutaneous coronary artery stent implantation has become a routine way to treat coronary heart disease. Although studies have shown how a drug-eluting stent could improve the efficacy of clinical treatment, 10~20% of in-stent restenosis is still an important outcome that restricts the clinical efficacy of drug-eluting stent implantations and causes cardiovascular events such as angina pectoris, acute myocardial infarction, and sudden death. The KCa3.1 channel plays an important role in neoatherosclerosis of in-stent restenosis by regulating macrophage function. Recent studies have shown that the KCa3.1 channel, which belongs to the family of calcium-activated potassium channels, plays an important role in the occurrence and development of various inflammatory diseases by regulating cell membrane potentials and calcium signaling in the processes of macrophage migration and mitogen-stimulated vascular smooth muscle cell and fibroblast proliferation. The KCa3.1 channel is activated by elevated intracellular calcium levels. Inhibition of the KCa3.1 channel can effectively slow the progression of arterial plaque rupture and reduce the degree of vascular restenosis, and so substances that can carry out this inhibition are expected to become targeted drugs for the treatment of in-stent neoatherosclerosis. This article reviews the pathological and physiological roles of the KCa3.1 channel and its roles in the disease prognosis of in-stent neoatherosclerosis.

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Abbreviations

AMI:

Acute myocardial infarction

AP-1:

Activator protein-1

bFGF:

Basic fibroblast growth factor

BMS:

Bare metal stents

CHD:

Coronary heart disease

DES:

Drug-eluting stent

EDHF:

Endothelium-derived hyperpolarization factor

fMLP:

Formyl-Met-Leu-Phe

IFN-α:

Interferon alpha

ISNA:

In-stent neoatherosclerosis

ISR:

In-stent restenosis

KCa3.1 channel:

Intermediate-conductance Ca2+-activated K+ channels

LST:

Late-stent thrombosis

MCP-1:

Macrophage chemotactic protein 1

NFAT:

Nuclear factor of activated T cells

PTCA:

Percutaneous coronary angioplasty

PCI:

Percutaneous coronary intervention

PDGF:

Platelet-derived growth factor

MACE:

Sudden cardiac death

VSMC:

Vascular smooth muscle cell

TCR:

T cell receptor

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Funding

This study was supported by the National Natural Science Foundation of China (81370304); Natural Science Foundation of Jiangsu Province (BK20151085); Jiangsu Provincial Key Research and Development Program (BE2018611); the 10th Summit of Six Top Talents of Jiangsu Province (2016-WSN-185); and Medical Science and technology development Foundation of Nanjing Department of Health (YKK15101, ZKX16048).

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  1. Yan-Rong Zhu and Xiao-Xin Jiang contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, Jiangsu, China

    Yan-Rong Zhu, Xiao-Xin Jiang & Dai-Min Zhang

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  1. Yan-Rong Zhu
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  2. Xiao-Xin Jiang
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  3. Dai-Min Zhang
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Correspondence to Dai-Min Zhang.

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Zhu, YR., Jiang, XX. & Zhang, DM. Critical regulation of atherosclerosis by the KCa3.1 channel and the retargeting of this therapeutic target in in-stent neoatherosclerosis. J Mol Med 97, 1219–1229 (2019). https://doi.org/10.1007/s00109-019-01814-9

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  • DOI: https://doi.org/10.1007/s00109-019-01814-9

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