摘要
Considerable evidence indicates that type 1 T helper （Th 1）- and Th 17-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 Thl 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 Thl ceils 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.
Considerable evidence indicates that type 1 T helper （Th 1）- and Th 17-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 Thl 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 Thl ceils 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.
基金
Our study was supported by the National ＇973＇ Program of China （2011CB503900）, the National Natural Science Foundation of China （30628015, 30700729, and 30872309） and Natural Science foundation of Shandong （Z2008C02）.
