Stat5 Conditional Knockout In T Cells Delay The Atherosclerosis Progression Through Reducing Inflammation And Regulate Cholesterol Metabolism In Apoe-deficiency Mice Model

Atherosclerosis is the underlying basis for most cardiovascular diseases.It is a chronic inflammatory disease characterized by the accumulation of lipid-loaded macrophages in the arterial wall.Recent studies demonstrated that T cell infiltrates into aorta plaque and plays an important role in recruiting macrophages to the vascular wall.In T cell,STAT5（Signal Transducer and Activator of Transcription 5）is a central coordinator of inflammatory responses through cytokine activation and is implicated in the T cell subsets development.However,whether STAT5 in T cell regulates the development of atherosclerosis remained unknown.Here we found that in the high-cholesterol-high-fat-diet（HFD）-induced atherosclerosis mice model,Stat5-conditonal Knockout in CD4⁺T cells(Stat5^CD4KO)resulted in lower inflammation level and had fewer CD4⁺T cells in spleen and blood.Surprisingly,Stat5^CD4KO displayed reduced serum cholesterol level at the advance atherosclerosis stage,which contributed to the amelioration of the atherosclerosis pathology.We found that Stat5^CD4KO mice reduced the serum cholesterol level by increasing hepatic cholesterol uptake/metabolism.To sum up,our work discovered that loss of Stat5 in T cell ameliorates atherosclerosis symptoms via two independent pathways:it not only directly reduces the local vascular inflammatory level,but also lowers the serum cholesterol level via the crosstalk between T cells and hepatic cells.Therefore,STAT5 could be a promising drug target to treat atherosclerosis through suppressing inflammation and regulating cholesterol.