Biology subjects

Reusswig, F.

Publications and source records attributed to Reusswig, F..

3 recordsLinked to original sources

bioRxiv2024

Platelets induce cell apoptosis of cardiac cells via FasL after acute myocardial infarction

Acute myocardial infarction (AMI) is one of the leading causes of death worldwide. Cell apoptosis in the myocardium plays an important role in ischemia and reperfusion (I/R) injury, leading to cardiac damage and dysfunction. Platelets are major players of hemostasis and play a crucial role in vessel occlusion, inflammation and cardiac remodeling after I/R. Here, we studied the impact of platelets on cell apoptosis in the myocardium using a close-chest mouse model of AMI. We found caspase-3 positive resident cardiac cells while leukocytes were negative for caspase-3. Using two different mouse models of thrombocytopenia, we detected a significant reduction of caspase-3 positive cells in the infarct border zone after I/R injury. Further, we identified platelet FasL to induce cell apoptosis via the extrinsic pathway of Fas receptor activation of target cells. Mechanistically, hypoxia triggers platelet adhesion to FasR suggesting that platelet induced apoptosis is elevated after I/R. Platelet-specific FasL knock-out mice showed reduced Bax and BcL-2 expression suggesting that platelets modulate the intrinsic and the extrinsic pathway of apoptosis leading to reduced infarct size after myocardial I/R injury. Therefore, platelet induced cardiac damage needs to be taken into account while optimizing antithrombotic/antiplatelet strategies for patients with AMI.

molecular biology↗

bioRxiv2024

Crosstalk between thrombospondin-1 and CD36 modulates platelet-RBC interaction limiting thrombosis and abdominal aneurysm formation

Red blood cells (RBCs) contribute to hemostasis and thrombosis by interaction with platelets via the FasL-FasR pathway to induce procoagulant activity and thrombin formation. Here, we identified a novel mechanism of platelet-RBC interaction via the CD36-thrombospondin-1 (TSP-1) signaling pathway, which is important in thrombus formation and the recruitment of RBCs to collagen-adherent platelets. Platelet-released TSP-1 can bind to CD36 at the RBC membrane to enhance procoagulant activity and to increase the activation of integrin IIb{beta}3, which represents an additional ligand for erythroid FasR, suggesting that both mechanisms of platelet-RBC interaction act in concert to propagate thrombus formation. In patients with abdominal aortic aneurysm (AAA), enhanced procoagulant activity of RBCs and platelets is accompanied by elevated exposure of TSP-1 and FasL at the platelet surface and accumulation of TSP-1 in the aortic wall and the intraluminal thrombus, suggesting that platelet-RBC interaction plays an important role in AAA pathology. TSP-1-deficient mice are protected against aortic diameter expansion in an experimental model of AAA, highlighting the crucial role of the CD36-TSP-1 axis in AAA. Thus, interfering with platelet-RBC interaction may be a promising therapeutic approach to reduce pro-coagulant activity and preserve AAA patients from surgery or rupture.

pathology↗

bioRxiv2022

Platelet pannexin-1 channels modulate inflammation during abdominal aortic aneurysm formation

Abdominal aortic aneurysm (AAA) is a common disease and highly lethal if untreated. The progressive dilatation of the abdominal aorta is accompanied by degradation and remodeling of the vessel wall due to chronic inflammation. Pannexins represent anion-selective channels and play a crucial role in non-vesicular ATP release to amplify paracrine signaling in cells. Thus, pannexins are involved in many (patho-) physiological processes. Recently, Panx1 channels were identified to be significantly involved in AAA formation through endothelial derived Panx1 regulated inflammation and aortic remodeling. In platelets, Panx1 becomes activated following activation of glycoprotein (GP)VI. Since platelets play a role in cardiovascular diseases including AAA, we analyzed the contribution of platelet Panx1 in the progression of AAA. We detected enhanced Panx1 plasma levels in AAA patients. In experimental AAA using the pancreatic porcine elastase (PPE) mouse model, a major contribution of platelet Panx1 channels in platelet activation, pro-coagulant activity of platelets and platelet-mediated inflammation has been detected. In detail, platelets are important for the migration of neutrophils into the aortic wall induced by direct cell interaction and by activation of endothelial cells. Decreased platelet activation and inflammation did not affect ECM remodeling or wall thickness in platelet-specific Panx1 knock-out mice following PPE surgery. Thus, aortic diameter expansion at different time points after elastase infusion of the aortic wall was unaltered in platelet-specific Panx1 deficient mice suggesting that the modulation of inflammation alone does not affect AAA formation and progression. In conclusion, our data strongly supports the role of platelets in inflammatory responses in AAA via Panx1 channels and adds important knowledge about the significance of platelets in AAA pathology important for the establishment of an anti-platelet therapy for AAA patients.

cell biology↗