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Resistin is secreted from macrophages in atheromas and promotes atherosclerosis
Hye Seung Jung1, Ki-Ho Park, Young Min Cho
1Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-744, South Korea.
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.
Insights
Macrophages in atherosclerotic aneurysms secrete resistin, a protein that impacts vascular endothelial cells and smooth muscle cells, potentially contributing to atherosclerosis development.
Area of Science:
- Cardiovascular Biology
- Immunology
- Molecular Medicine
Background:
- Resistin is a secreted polypeptide primarily produced by human monocytes/macrophages.
- Elevated resistin levels have been linked to vascular endothelial dysfunction and smooth muscle cell proliferation.
- The local secretion and vascular effects of resistin in human atheromas were previously unclear.
Purpose of the Study:
- To investigate whether resistin is secreted by macrophages within human atheromas.
- To determine the impact of resistin on human vascular endothelial cells (HUVECs) and vascular smooth muscle cells (VSMCs).
Main Methods:
- Immunohistochemistry and immunofluorescence were used to detect resistin and macrophage markers in human aortic aneurysms.
- Resistin mRNA expression was compared in cultured monocytes/macrophages, VSMCs, and HUVECs.
- HUVECs and VSMCs were treated with resistin to assess effects on plasminogen activator inhibitor (PAI)-1, endothelin (ET)-1, and VSMC migration.
Main Results:
- Resistin-positive staining co-localized with macrophage infiltration (CD68) in human aortic aneurysms, but not in normal arteries.
- Resistin mRNA expression was significantly higher in macrophages compared to VSMCs and HUVECs.
- Resistin treatment increased PAI-1 and ET-1 mRNA levels in HUVECs and enhanced VSMC migration.
Conclusions:
- Macrophages infiltrating atherosclerotic lesions secrete resistin locally.
- Resistin influences endothelial cell function and promotes vascular smooth muscle cell migration.
- Macrophage-derived resistin may play a role in the pathogenesis of atherosclerosis.
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