【medical-news】ADA2013-血管内皮细胞IRS1的过度表达以及胰岛素水平提高可减少粥样硬化
发布于 2013-06-26 · 浏览 1176 · IP 美国美国
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血管内皮细胞IRS1的过度表达以及胰岛素水平提高可减少粥样硬化
Authors
Kyoungmin Park PhD
Loss of insulin receptors or actions on the endotheliumcontributes to the increased risk of atherosclerosis. However，no study has documented that enhancement of insulin signalingdirectly in theendothelium can decrease atherosclerosis in normal or insulinresistant states.
To enhance insulin's antiatherogenic action via PI3K/Akt/eNOSpathway we generated transgenic mice overexpressing IRS1 on ApoE/- background(IRS1/ApoE/- mice) driven by endothelial specific VEcadherin promoter.Immunoblot and immunocytochemistry assay confirmed that IRS1 is specificallyoverexpressed in endothelial cells and aorta by 2.7fold. Insulin signaling inthe femoral artery showed an enhancement on the activation of p-Akt/eNOS by2.5-fold in IRS1/ApoE-/- vs ApoE-/-mice.
Quantitation of the atheroscleroticplaque by en face staining after 24 weeks of high fat diet (HFD 42%) showed areduction of plaque by 46% ± 11% (p<0.05). Complexity of the plaque showed areduction of plaque size by 40% ± 20% (p<0.05) extracellular matrix by 37% ±14% (p<0.05) smooth muscle cell numbers by 27% ± 7% (p<0.05) andmacrophage content by 33% ± 11% (p<0.05). Expression of VCAM1 and ICA1mRNA levels were also decreased by 53% ± 17% and 47% ± 13% respectively(p<0.05) whereas the levels of p-eNOS were increased by 3.6-fold inIRS1/ApoE-/- vs. ApoE-/- mice.
Functional studies measured by leukocyteendothelial cellbinding when stimulated by oxidized LDL exhibited a reduction of 43% ± 20% inIRS1/ApoE/vs ApoE/- mice. This study provided the first demonstration thatenhancing insulin activities via IRS1/Akt pathway can decrease HFDinduced atherosclerosis.These findings also supported the exciting possibility that targeting insulinto activate IRS1/Akt pathway on the endothelium will reduce the risk ofatherosclerosis in diabetes and insulin resistant states.
Authors
Kyoungmin Park PhD
Loss of insulin receptors or actions on the endotheliumcontributes to the increased risk of atherosclerosis. However，no study has documented that enhancement of insulin signalingdirectly in theendothelium can decrease atherosclerosis in normal or insulinresistant states.
To enhance insulin's antiatherogenic action via PI3K/Akt/eNOSpathway we generated transgenic mice overexpressing IRS1 on ApoE/- background(IRS1/ApoE/- mice) driven by endothelial specific VEcadherin promoter.Immunoblot and immunocytochemistry assay confirmed that IRS1 is specificallyoverexpressed in endothelial cells and aorta by 2.7fold. Insulin signaling inthe femoral artery showed an enhancement on the activation of p-Akt/eNOS by2.5-fold in IRS1/ApoE-/- vs ApoE-/-mice.
Quantitation of the atheroscleroticplaque by en face staining after 24 weeks of high fat diet (HFD 42%) showed areduction of plaque by 46% ± 11% (p<0.05). Complexity of the plaque showed areduction of plaque size by 40% ± 20% (p<0.05) extracellular matrix by 37% ±14% (p<0.05) smooth muscle cell numbers by 27% ± 7% (p<0.05) andmacrophage content by 33% ± 11% (p<0.05). Expression of VCAM1 and ICA1mRNA levels were also decreased by 53% ± 17% and 47% ± 13% respectively(p<0.05) whereas the levels of p-eNOS were increased by 3.6-fold inIRS1/ApoE-/- vs. ApoE-/- mice.
Functional studies measured by leukocyteendothelial cellbinding when stimulated by oxidized LDL exhibited a reduction of 43% ± 20% inIRS1/ApoE/vs ApoE/- mice. This study provided the first demonstration thatenhancing insulin activities via IRS1/Akt pathway can decrease HFDinduced atherosclerosis.These findings also supported the exciting possibility that targeting insulinto activate IRS1/Akt pathway on the endothelium will reduce the risk ofatherosclerosis in diabetes and insulin resistant states.
最后编辑于 2013-06-26 · 浏览 1176
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