Th17 cells and IL-17 are involved in the disruption of vulnerable plaques triggered by short-term combination stimulation in apolipoprotein E-knockout mice.

Abstract

Considerable evidence indicates that type 1 T helper (Th1)- and Th17-mediated immune responses promote the formation of atherosclerotic plaques while that CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) have a protective effect. However, the functions of diverse CD4(+) lymphocyte subsets in plaque rupture remain poorly understood because of a shortage of satisfactory plaque rupture models. Here, we established a murine model of atherosclerotic plaque rupture using a high-fat diet and collar placement on the carotid artery, and triggered plaque rupture by short-term stimulation with a combination of lipopolysaccharide, phenylephrine injection and cold in apolipoprotein E-knockout (ApoE(-/-)) mice. We investigated the associations between Th1 cells, Th17 cells and Tregs and plaque rupture by PCR, flow cytometry, ELISA and immunohistochemistry. In total, 75% (18/24) of vulnerable plaques, but no stable plaques, showed rupture characteristics. The proportion of Th17 cells was increased among splenocytes after treatment, but the changes in the levels of Th1 cells and Tregs were not related to rupture. Furthermore, the treatment resulted in high levels of interleukin-17 (IL-17) in the serum and in the region of plaque rupture. In vitro, IL-17 increased the level of apoptosis, a major factor associated with plaque rupture, in cultured murine vascular smooth muscle cells. Th17 cells and IL-17 may be involved in the disruption of vulnerable plaques triggered by short-term stimulation with lipopolysaccharide, phenylephrine injection and cold in ApoE(-/-)mice.

• Authors: Tian Ma, Qi Gao, Faliang Zhu, Chun Guo, Qun Wang, Fei Gao, Lining Zhang
• Journal: Cellular & molecular immunology (Cell Mol Immunol) Vol. 10 Issue 4 Pg. 338-48 (Jul 2013) ISSN: 2042-0226 [Electronic] China
• PMID: 23542316 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• CD4 Antigens
• Forkhead Transcription Factors
• Foxp3 protein, mouse
• Interleukin-17
• Interleukin-2 Receptor alpha Subunit
• Lipopolysaccharides
• Phenylephrine

Topics

• Animals
• Apolipoproteins E (genetics)
• CD4 Antigens (metabolism)
• Carotid Arteries (drug effects, immunology, pathology)
• Cells, Cultured
• Cold Temperature
• Diet, High-Fat
• Disease Models, Animal
• Forkhead Transcription Factors (metabolism)
• Humans
• Interleukin-17 (blood, immunology)
• Interleukin-2 Receptor alpha Subunit (metabolism)
• Lipopolysaccharides (administration & dosage)
• Male
• Mice
• Mice, Knockout
• Myocytes, Smooth Muscle (drug effects, immunology, pathology)
• Phenylephrine (administration & dosage)
• Plaque, Atherosclerotic (chemically induced, immunology, pathology)
• T-Lymphocytes, Regulatory (immunology)
• Th1 Cells (immunology)
• Th17 Cells (immunology)