Effect of the Kv1.3 voltage-gated potassium channel blocker PAP-1 on the initiation and progress of atherosclerosis in a rat model.
Acute coronary syndrome is a serious medical emergency. It occurs when an atherosclerotic plaque ruptures, leading to thrombus formation within a coronary artery. Previous studies have shown that T cells are involved in the initiation and progression of acute coronary syndrome. CD4(+)CD28(null) T lymphocytes increase in atherosclerotic plaque, and voltage-gated potassium channel Kv1.3 blockers can suppress the function of these cells in vitro by preventing exocytosis of their cytoplasmic granules. The purpose of this study was to investigate the effect of PAP-1, a small molecule voltage-gated potassium channel Kv1.3 blocker, on the development of atherosclerosis (AS) in a rat model and the potential mechanism for this effect. Plasma lipids, interferonγ, CRP, CD4(+)CD28(null) T cells, and perforin were increased and unstable atherosclerotic plaques developed in the rat model of AS. Blockade of the Kv1.3 potassium channel via PAP-1 administration decreased perforin levels and prevented plaque formation but had no effect on the other changes seen in this AS model. These findings suggest that the small molecule, voltage-gated potassium channel Kv1.3 blocker PAP-1 can suppress the development of AS in a rat model, most likely by inhibiting the exocytosis of cytoplasmic granules from CD4(+)CD28(null) T cells.
Department of Gerontology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China, happyxiao832@hotmail.com.
Xiaofen
X
Wu
Rende
R
Xu
Ming
M
Cao
Lei
L
Ruan
Xingfen
X
Wang
Cuntai
C
Zhang
D054058:Acute Coronary Syndrome / Q000209:etiology; D000800:Angioplasty, Balloon; D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D050197:Atherosclerosis / Q000150:complications / Q000188:drug therapy*; D002097:C-Reactive Protein / Q000032:analysis; D017536:Carotid Artery, Common; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000097:blood; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors*; D008055:Lipids / Q000097:blood; D008297:Male; D000073718:Pancreatitis-Associated Proteins; D054353:Perforin / Q000097:blood; D058226:Plaque, Atherosclerotic / Q000517:prevention & control*; D026902:Potassium Channel Blockers / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000276:immunology*
D051664:Kv1.3 Potassium Channel; D008055:Lipids; D000073718:Pancreatitis-Associated Proteins; D026902:Potassium Channel Blockers; C000612141:REG3A protein, human; D054353:Perforin; D007371:Interferon-gamma; D002097:C-Reactive Protein