Adipokine resistin is a key player to modulate monocytes, endothelial cells, and smooth muscle cells, leading to progression of atherosclerosis in rabbit carotid artery

Youngjin Cho, Sang Eun Lee, Hyun Chae Lee, Jin Hur, Sahmin Lee, Seock Won Youn, Jaewon Lee, Ho Jae Lee, Tae Kyu Lee, Jonghanne Park, Seok Jae Hwang, Yoo Wook Kwon, Hyun Jai Cho, Byung Hee Oh, Young Bae Park, Hyo Soo Kim

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Objectives We investigated the effects of human resistin on atherosclerotic progression and clarified its underlying mechanisms. Background Resistin is an adipokine first identified as a mediator of insulin resistance in murine obesity models. But, its role in human pathology is under debate. Although a few recent studies suggested the relationship between resistin and atherosclerosis in humans, the causal relationship and underlying mechanism have not been clarified. Methods We cloned rabbit resistin, which showed 78% identity to human resistin at the complementary deoxyribonucleic acid level, and its expression was examined in 3 different atherosclerotic rabbit models. To evaluate direct role of resistin on atherosclerosis, collared rabbit carotid arteries were used. Histological and cell biologic analyses were performed. Results Rabbit resistin was expressed by macrophages of the plaque in the 3 different atherosclerotic models. Peri-adventitial resistin gene transfer induced macrophage infiltration and expression of various inflammatory cytokines, resulting in the acceleration of plaque growth and destabilization. In vitro experiments elucidated that resistin increased monocyte-endothelial cell adhesion by upregulating very late antigen-4 on monocytes and their counterpart vascular cell adhesion molecule-1 on endothelial cells. Resistin augmented monocyte infiltration in collagen by direct chemoattractive effect as well as by enhancing migration toward monocyte chemotactic protein-1. Administration of connecting segment-1 peptide, which blocks very late antigen-4 × vascular cell adhesion molecule-1 interaction, ameliorated neointimal growth induced by resistin in vivo. Conclusions Our results indicate that resistin aggravates atherosclerosis by stimulating monocytes, endothelial cells, and vascular smooth muscle cells to induce vascular inflammation. These findings provide the first insight on the causal relationship between resistin and atherosclerosis.

Original languageEnglish (US)
Pages (from-to)99-109
Number of pages11
JournalJournal of the American College of Cardiology
Volume57
Issue number1
DOIs
StatePublished - Jan 4 2011

Fingerprint

Resistin
Adipokines
Carotid Arteries
Smooth Muscle Myocytes
Monocytes
Atherosclerosis
Endothelial Cells
Rabbits
Integrin alpha4beta1
Vascular Cell Adhesion Molecule-1
Macrophages
Adventitia
Chemokine CCL2
Growth
Vascular Smooth Muscle
Cell Adhesion
Blood Vessels
Insulin Resistance
Collagen
Obesity

Keywords

  • atherosclerosis
  • inflammation
  • resistin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Adipokine resistin is a key player to modulate monocytes, endothelial cells, and smooth muscle cells, leading to progression of atherosclerosis in rabbit carotid artery. / Cho, Youngjin; Lee, Sang Eun; Lee, Hyun Chae; Hur, Jin; Lee, Sahmin; Youn, Seock Won; Lee, Jaewon; Lee, Ho Jae; Lee, Tae Kyu; Park, Jonghanne; Hwang, Seok Jae; Kwon, Yoo Wook; Cho, Hyun Jai; Oh, Byung Hee; Park, Young Bae; Kim, Hyo Soo.

In: Journal of the American College of Cardiology, Vol. 57, No. 1, 04.01.2011, p. 99-109.

Research output: Contribution to journalArticle

Cho, Y, Lee, SE, Lee, HC, Hur, J, Lee, S, Youn, SW, Lee, J, Lee, HJ, Lee, TK, Park, J, Hwang, SJ, Kwon, YW, Cho, HJ, Oh, BH, Park, YB & Kim, HS 2011, 'Adipokine resistin is a key player to modulate monocytes, endothelial cells, and smooth muscle cells, leading to progression of atherosclerosis in rabbit carotid artery', Journal of the American College of Cardiology, vol. 57, no. 1, pp. 99-109. https://doi.org/10.1016/j.jacc.2010.07.035
Cho, Youngjin ; Lee, Sang Eun ; Lee, Hyun Chae ; Hur, Jin ; Lee, Sahmin ; Youn, Seock Won ; Lee, Jaewon ; Lee, Ho Jae ; Lee, Tae Kyu ; Park, Jonghanne ; Hwang, Seok Jae ; Kwon, Yoo Wook ; Cho, Hyun Jai ; Oh, Byung Hee ; Park, Young Bae ; Kim, Hyo Soo. / Adipokine resistin is a key player to modulate monocytes, endothelial cells, and smooth muscle cells, leading to progression of atherosclerosis in rabbit carotid artery. In: Journal of the American College of Cardiology. 2011 ; Vol. 57, No. 1. pp. 99-109.
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abstract = "Objectives We investigated the effects of human resistin on atherosclerotic progression and clarified its underlying mechanisms. Background Resistin is an adipokine first identified as a mediator of insulin resistance in murine obesity models. But, its role in human pathology is under debate. Although a few recent studies suggested the relationship between resistin and atherosclerosis in humans, the causal relationship and underlying mechanism have not been clarified. Methods We cloned rabbit resistin, which showed 78{\%} identity to human resistin at the complementary deoxyribonucleic acid level, and its expression was examined in 3 different atherosclerotic rabbit models. To evaluate direct role of resistin on atherosclerosis, collared rabbit carotid arteries were used. Histological and cell biologic analyses were performed. Results Rabbit resistin was expressed by macrophages of the plaque in the 3 different atherosclerotic models. Peri-adventitial resistin gene transfer induced macrophage infiltration and expression of various inflammatory cytokines, resulting in the acceleration of plaque growth and destabilization. In vitro experiments elucidated that resistin increased monocyte-endothelial cell adhesion by upregulating very late antigen-4 on monocytes and their counterpart vascular cell adhesion molecule-1 on endothelial cells. Resistin augmented monocyte infiltration in collagen by direct chemoattractive effect as well as by enhancing migration toward monocyte chemotactic protein-1. Administration of connecting segment-1 peptide, which blocks very late antigen-4 × vascular cell adhesion molecule-1 interaction, ameliorated neointimal growth induced by resistin in vivo. Conclusions Our results indicate that resistin aggravates atherosclerosis by stimulating monocytes, endothelial cells, and vascular smooth muscle cells to induce vascular inflammation. These findings provide the first insight on the causal relationship between resistin and atherosclerosis.",
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T1 - Adipokine resistin is a key player to modulate monocytes, endothelial cells, and smooth muscle cells, leading to progression of atherosclerosis in rabbit carotid artery

AU - Cho, Youngjin

AU - Lee, Sang Eun

AU - Lee, Hyun Chae

AU - Hur, Jin

AU - Lee, Sahmin

AU - Youn, Seock Won

AU - Lee, Jaewon

AU - Lee, Ho Jae

AU - Lee, Tae Kyu

AU - Park, Jonghanne

AU - Hwang, Seok Jae

AU - Kwon, Yoo Wook

AU - Cho, Hyun Jai

AU - Oh, Byung Hee

AU - Park, Young Bae

AU - Kim, Hyo Soo

PY - 2011/1/4

Y1 - 2011/1/4

N2 - Objectives We investigated the effects of human resistin on atherosclerotic progression and clarified its underlying mechanisms. Background Resistin is an adipokine first identified as a mediator of insulin resistance in murine obesity models. But, its role in human pathology is under debate. Although a few recent studies suggested the relationship between resistin and atherosclerosis in humans, the causal relationship and underlying mechanism have not been clarified. Methods We cloned rabbit resistin, which showed 78% identity to human resistin at the complementary deoxyribonucleic acid level, and its expression was examined in 3 different atherosclerotic rabbit models. To evaluate direct role of resistin on atherosclerosis, collared rabbit carotid arteries were used. Histological and cell biologic analyses were performed. Results Rabbit resistin was expressed by macrophages of the plaque in the 3 different atherosclerotic models. Peri-adventitial resistin gene transfer induced macrophage infiltration and expression of various inflammatory cytokines, resulting in the acceleration of plaque growth and destabilization. In vitro experiments elucidated that resistin increased monocyte-endothelial cell adhesion by upregulating very late antigen-4 on monocytes and their counterpart vascular cell adhesion molecule-1 on endothelial cells. Resistin augmented monocyte infiltration in collagen by direct chemoattractive effect as well as by enhancing migration toward monocyte chemotactic protein-1. Administration of connecting segment-1 peptide, which blocks very late antigen-4 × vascular cell adhesion molecule-1 interaction, ameliorated neointimal growth induced by resistin in vivo. Conclusions Our results indicate that resistin aggravates atherosclerosis by stimulating monocytes, endothelial cells, and vascular smooth muscle cells to induce vascular inflammation. These findings provide the first insight on the causal relationship between resistin and atherosclerosis.

AB - Objectives We investigated the effects of human resistin on atherosclerotic progression and clarified its underlying mechanisms. Background Resistin is an adipokine first identified as a mediator of insulin resistance in murine obesity models. But, its role in human pathology is under debate. Although a few recent studies suggested the relationship between resistin and atherosclerosis in humans, the causal relationship and underlying mechanism have not been clarified. Methods We cloned rabbit resistin, which showed 78% identity to human resistin at the complementary deoxyribonucleic acid level, and its expression was examined in 3 different atherosclerotic rabbit models. To evaluate direct role of resistin on atherosclerosis, collared rabbit carotid arteries were used. Histological and cell biologic analyses were performed. Results Rabbit resistin was expressed by macrophages of the plaque in the 3 different atherosclerotic models. Peri-adventitial resistin gene transfer induced macrophage infiltration and expression of various inflammatory cytokines, resulting in the acceleration of plaque growth and destabilization. In vitro experiments elucidated that resistin increased monocyte-endothelial cell adhesion by upregulating very late antigen-4 on monocytes and their counterpart vascular cell adhesion molecule-1 on endothelial cells. Resistin augmented monocyte infiltration in collagen by direct chemoattractive effect as well as by enhancing migration toward monocyte chemotactic protein-1. Administration of connecting segment-1 peptide, which blocks very late antigen-4 × vascular cell adhesion molecule-1 interaction, ameliorated neointimal growth induced by resistin in vivo. Conclusions Our results indicate that resistin aggravates atherosclerosis by stimulating monocytes, endothelial cells, and vascular smooth muscle cells to induce vascular inflammation. These findings provide the first insight on the causal relationship between resistin and atherosclerosis.

KW - atherosclerosis

KW - inflammation

KW - resistin

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