Platelet-specific TGFβ1 deficiency aggravates atherosclerosis, vascular inflammation, and hypercholesterolemia in mice
bioRxiv (Cold Spring Harbor Laboratory)(2023)
摘要
Atherosclerosis involves inflammatory and thrombotic mechanisms, to which both platelets and transforming growth factor β (TGFβ) contribute. The effect of platelet-derived TGFβ on atherosclerosis is, however, unknown and therefore investigated. Murine platelet-selective TGFβ-deficiency (plt-TGFβ-/-) was created by a Pf4-Cre approach, and an atherosclerotic mouse model was established by functional abrogation of Ldlr and 10-15 weeks of a high-fat diet in plt-TGFβ-/- mice and their non-plt-TGFβ-/- littermates. En face Oil Red O staining of the aorta showed more atherosclerotic lesion formation in plt-TGFβ-/- mice, with significant increases in both lesion size and lesion coverage of the total aortic area. Cryosections of the aortic root confirmed the aggravation of atherogenesis. Platelet-derived TGFβ deficiency increased circulating platelets and plasma levels of total cholesterol, LDL-cholesterol, and triglycerides after a 10 or 15 week high-fat diet period. RNA sequencing and proteomic analyses of the aorta showed signs of CD4+ T effector cell and macrophage activation in plt-TGFβ-/- mice. In conclusion, platelet-specific TGFβ deficiency aggravates atherosclerosis, via increasing arterial inflammation and plasma levels of cholesterol. Our findings demonstrate that platelet-derived TGFβ is prominently athero-protective.
### Competing Interest Statement
The authors have declared no competing interest.
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关键词
atherosclerosis,vascular inflammation,hypercholesterolemia,platelet-specific
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