Copyright © 2005, European Society of Cardiology
Resistin is secreted from macrophages in atheromas and promotes atherosclerosis
aDepartment of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-744, South Korea
bGenome Research Center for Diabetes and Endocrine Disease, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea
cDepartment of Pathology, Seoul National University College of Medicine, Seoul, South Korea
dDepartment of Surgery, Seoul National University College of Medicine, Seoul, South Korea
* Corresponding author. Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-744, South Korea. Tel.: +82 2 2072 1789; fax: +82 2 3676 8309. Email address: kspark{at}snu.ac.kr
Objective: Resistin belongs to a family of cysteine-rich secreted polypeptides that are mainly produced by monocytes/macrophages in humans. Recently, high concentrations of resistin were shown to induce vascular endothelial dysfunction and vascular smooth muscle cell proliferation. We examined if resistin was secreted from macrophages locally in atheromas and if it affected vascular cell function in human.
Methods and results: Immunohistochemical staining of human vessels showed that aortic aneurysms exhibited resistin-positive staining areas along macrophage infiltration, while normal arteries and veins did not. Co-localization of resistin and CD68 (a marker for macrophages) was observed in immunofluorescent double staining of aneurysms. Resistin mRNA was expressed much higher in cultured monocytes/macrophages than in human vascular smooth muscle cells (VSMCs) and human umbilical venous endothelial cells (HUVECs). This suggested that the resistin in aneurysms originates from macrophages within the vessels. To determine the effects of resistin on atherosclerosis, HUVECs and human VSMCs were incubated with resistin (10–100 ng/mL for 4
24 h). In HUVECs, plasminogen activator inhibitor (PAI)-1 release was assayed by ELISA, while the PAI-1 and endothelin (ET)-1 mRNA levels were analyzed by Northern blotting. Both were increased significantly with resistin treatment by factors of 1.3–2.5 (p<0.05). Migratory activity of VSMCs measured by scratched wound assay also increased significantly (1.6 times, p<0.05). In summary, macrophages infiltrating atherosclerotic aneurysms secrete resistin, and resistin affects endothelial function and VSMC migration.
Conclusions: Resistin secreted from macrophages may contribute to atherogenesis by virtue of its effects on vascular endothelial cells and smooth muscle cells in humans.
KEYWORDS Resistin; Macrophages; Atherosclerosis; PAI-1; Migration
Abbreviations: AAA, abdominal aortic aneurysm • BMI, body mass index=weight in kilogram/height in square meter • Ct, threshold cycle • DM, diabetes mellitus • ELISA, enzyme-linked immunosorbent assay • ET-1, endothelin type 1 • FACS, Fluorescence-activated cell sorting • FBS, fetal bovine serum • GAPDH, glyceraldehyde-3-phosphate dehydrogenase • HT, hypertension • HUVECs, human umbilical venous endothelial cells • IF, immunofluorescent • IHC, immunohistochemical • mAb, monoclonal antibody • PAI-1, plasminogen activator inhibitor type 1 • PPAR, peroxisome proliferator-activated receptor • RT-PCR, reverse transcriptase-polymerase chain reaction • TNF, tumor necrosis factor • VSMCs, vascular smooth muscle cells
Time for primary review 18 days
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