Diabetologia: Dapagliflozin reduces the cardiovascular risk of type 2 diabetes by reducing thrombin production and platelet activation

Objective: Diabetes patients have increased cardiovascular risk, accelerated development of atherosclerosis, and increased mortality after myocardial infarction

Diabetes patients increase cardiovascular risk, accelerate the development of atherosclerosis, and increase mortality after myocardial infarction

L dlr ^−/−

Metabolic measurement: The body weight of the mice is evaluated once a week

Mouse platelet activation: In order to analyze the platelet activation markers CD62p (P-selectin) and CD41/61 (activated glycoprotein IIb/IIIa) by flow cytometry, the blood of Ldlr−/− mice was collected and collected in B2 In the test tube coated with ethylene glycol aminetetraacetate, wash twice and dilute to 1:10 in tyrosine buffer

Immune cell-platelet aggregation formation: flow cytometry detection, mouse blood is diluted in Tyrode buffer, centrifuged at 650g for 5 min, and washed twice

Results: Dapagliflozin treatment can improve the development of atherosclerotic lesions and reduce the platelet-leukocyte aggregation in the circulation (glycoprotein [GP]Ib ⁺ CD45 ⁺ : 29.

Reduce circulating platelet - leukocyte aggregation ^{+ + + +} Dag column net decrease the feed fed diabetes L L DLR DLR ^{- / -} - / - mouse activated CD62 the P- platelet but did not affect bleeding time Dag column net further reduced production of endogenous thrombin ^{-9 -9} thereby reducing one of the most important platelet activators Dag column net on isolated platelets direct inhibition thereof Dag column net increase the HDL-triazine - cholesterol levels higher HDL- cholesterol levels may Dag column net generation mediated platelet activation and inhibition of thrombin by Dag column reduces the platelet count net positive human CD62P treatment, without affecting hemostasis

 

Figure 1 Experimental environment

Figure 1 Experimental environment

Figure 2 Dapagliflozin can reduce atherosclerotic plaque burden, circulating platelet-leukocyte aggregation and macrophage infiltration in L dlr ^−/− mice

Figure 2 Dapagliflozin can reduce atherosclerotic plaque burden, circulating platelet-leukocyte aggregation and macrophage infiltration in L dlr ^−/− mice

Figure 3 Dapagliflozin reduces the expression of CD62P on activated platelets in healthy volunteers

Figure 3 Dapagliflozin reduces the expression of CD62P on activated platelets in healthy volunteers

Figure 4 The protective mechanism of atherosclerosis mediated by dapagliflozin

Figure 4 The protective mechanism of atherosclerosis mediated by dapagliflozin

We demonstrate that dapagliflozin-mediated atherosclerotic protection in mice is driven by high HDL-cholesterol and improvement of thrombin-platelet-mediated inflammation without interfering with hemostasis

Kohlmorgen C, Gerfer S, Feldmann K, et al.
Dapagliflozin reduces thrombin generation and platelet activation: implications for cardiovascular risk reduction in type 2 diabetes mellitus.
Diabetologia 2021 Aug;64(8)

Dapagliflozin reduces thrombin generation and platelet activation: implications for cardiovascular risk reduction in type 2 diabetes mellitus.


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