Hasil untuk "econ.TH"

Wolfgang Miesbach

AbstractThe activated renin–angiotensin system induces a prothrombotic state resulting from the imbalance between coagulation and fibrinolysis. Angiotensin II is the central effector molecule of the activated renin–angiotensin system and is degraded by the angiotensin-converting enzyme 2 to angiotensin (1–7). The novel coronavirus infection (classified as COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as acute respiratory distress syndrome, sepsis, and death in a proportion of patients, mostly elderly patients with preexisting comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor to enter the target cells, resulting in activation of the renin–angiotensin system. After downregulating the angiotensin-converting enzyme 2, the vasoconstrictor angiotensin II is increasingly produced and its counterregulating molecules angiotensin (1–7) reduced. Angiotensin II increases thrombin formation and impairs fibrinolysis. Elevated levels were strongly associated with viral load and lung injury in patients with severe COVID-19. Therefore, the complex clinical picture of patients with severe complications of COVID-19 is triggered by the various effects of highly expressed angiotensin II on vasculopathy, coagulopathy, and inflammation. Future treatment options should focus on blocking the thrombogenic and inflammatory properties of angiotensin II in COVID-19 patients.

Tony Walsh, Alastair Poole

AbstractPlatelets are classically known for their roles in bleeding control and occlusive thrombus formation causing ischemic tissue damage. Recently, nonclassical roles for platelets have been described, many of which may be mediated by the heterogeneous cargo that platelets secrete from granular stores upon activation. Using an in vitro model of ischemic injury to ventricular cardiomyocytes, we observed that platelets, through secreted factors, delayed the rate of cardiomyocyte death during ischemia. This protective effect appeared independent of platelet dense granule cargo, but required α-granule components stromal cell-derived factor-1α and transforming growth factor-β1. Protein kinase C activity within cardiomyocytes was responsible for mediating the protective signals initiated by the released platelet cargo. Importantly, pretreating platelets with a P2Y12 antagonist, but not the cyclooxygenase inhibitor aspirin, substantially attenuated this protective effect. These findings therefore reveal a paradoxically protective role for platelet activation during cardiac ischemia and could have important implications for the use of antiplatelet therapeutics in the management of myocardial infarction.

G. Wehnert, A. Sauerbrei, Th. Bayer et al.

M. Th. Mackowsky, Th. Nemetschek

Tanja Michalsky, Daniela Rywiková, Elisabetta Scirocco

Th. Förster, Th. Forster

C Th J ALKEMADE, Tj HOLLANDER, W SNELLEMAN et al.

Th. Schiemann

C.R. Broadus