Abstract Number: OC 01.5
Meeting: ISTH 2020 Congress
Background: Atherosclerosis and its cardiovascular and cerebrovascular complications are the most common causes of death, according to the latest data released by the WHO. And platelets take part in all stages of atherogenesis and especially in thrombus formation at the ruptured plaques. Therefore, to explore an effective prevention and novel therapeutic approaches are crucial and urgent.
Aims: We wanted to elucidate the impact of platelet specific TGF-β1-deficiency on atherogenesis and chronic CD4+ T cell immunity, using a no-germline genetic engineering atherosclerosis mouse model.
Methods: We established a murine strain with platelet-selective TGF-β1-deficiency “PF4-Cre+-TGF-β1f/f”. And then we established atherosclerotic mouse model via combining PCSK9-encoding rAAV8 vectors by tail vein injection and with a cholate-free Western-type high-fat diet. The time points were 10w and 15w after high-fat diet. We have measured many indicators, such as 1) Weight and heart weight; 2) Plasma TGF-β1; 3) Twenty two whole blood indicators including neutrophil, platelets, and etc.; 4) Ten correlated lipid level indicators including Cho, LDL-C, TG, and etc.; 5) Aorta en face staining and atherosclerotic lesions in the aortic root (Oil Red O staining); 6) Flow cytometry of spleen and lymph nodes including Th1, Treg, etc.; 7) PCR of spleens, and aortas; 8) IHC staining like CD4; and etc.
Results: We found that neutrophil, platelets, and lipid level of the experimental group increased significantly; the results of Oil Red O staining and flow cytometry analysis, and etc. together showed that atherosclerosis was aggravated in the experimental group obviously.
Conclusions: Platelets are an active and multifaceted engager in vascular inflammatory microenvironment. Platelet-derived TGF-β1 has an important protective effect for angiocarpy. True impacts of platelets on vascular microenvironment depend on the total readout of multiply factors. Future work is needed for the intervention strategy of platelet inflammatory activities.
To cite this abstract in AMA style:Tan S, Sun Y, Gisterå A, Min Y, Zhang J, Ma C, Li N. Impact of Platelet-Selective TGF-β1-Deficiency in Atherogenesis and CD4+ T Effector Responses Using a No-Germline Genetic Engineering Atherosclerosis Mouse Model [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/impact-of-platelet-selective-tgf-%ce%b21-deficiency-in-atherogenesis-and-cd4-t-effector-responses-using-a-no-germline-genetic-engineering-atherosclerosis-mouse-model/. Accessed September 24, 2021.
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