S-Space College of Medicine/School of Medicine (의과대학/대학원) Molecular and Genomic Medicine (분자유전체의학전공) Journal Papers (저널논문_분자유전체의학전공)
Resistin is secreted from macrophages in atheromas and promotes atherosclerosis
- Jung, Hye Seung; Park, Ki-Ho; Cho, Young Min; Chung, Sung Soo; Cho, Hyun Ju; Cho, Soo Youn; Kim, Sang Joon; Kim, Seong Yeon; Lee, Hong Kyu; Park, Kyong Soo
- Issue Date
- Oxford University Press
- Cardiovasc Res. 2006 Jan;69(1):76-85. Epub 2005 Nov 4.
- Actins/analysis; Aged; Antigens, CD/analysis; Antigens, CD31/analysis; Antigens, Differentiation, Myelomonocytic/analysis; Aortic Aneurysm, Abdominal/*immunology/metabolism; Atherosclerosis/*immunology/metabolism; Cells, Cultured; Endothelial Cells/metabolism; Endothelin-1/analysis/secretion; Fluorescent Antibody Technique; Humans; Immunohistochemistry/methods; Macrophages/*secretion; Male; Middle Aged; Muscle, Smooth, Vascular/metabolism; Myocytes, Smooth Muscle/metabolism; Plasminogen Activator Inhibitor 1/analysis/secretion; RNA, Messenger/analysis; Resistin/analysis/genetics/*secretion; Reverse Transcriptase Polymerase Chain Reaction
- 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 approximately 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.
- 0008-6363 (Print)
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