dad de la Rep lica, Montevideo 11800, Uruguay Correspondence: [email protected] (E.F.); [email protected] (S.W.); [email protected] (A.T.)Citation:

dad de la Rep lica, Montevideo 11800, Uruguay Correspondence: [email protected] (E.F.); [email protected] (S.W.); [email protected] (A.T.)Citation: Fuentes, E.; Wehinger, S.; Trostchansky, A. Regulation of Crucial Antiplatelet Pathways by Bioactive Compounds with Minimal CDK16 Molecular Weight bleeding Threat. Int. J. Mol. Sci. 2021, 22, 12380. doi.org/10.3390/ijms 222212380 Academic Editors: gel Garc and Alice Pollitt Received: 30 August 2021 Accepted: 20 September 2021 Published: 17 NovemberAbstract: Cardiovascular disease is strongly influenced by platelet activation. Platelet activation and thrombus formation at atherosclerotic plaque rupture web sites is often a dynamic method regulated by diverse signaling networks. As a result, there are actually now focused efforts to look for novel bioactive compounds which target receptors and pathways in the platelet activation process when preserving regular hemostatic function. The antiplatelet activity of various fruits and vegetables and their many mechanisms of action have lately been highlighted. Within this critique, we overview the antiplatelet actions of bioactive compounds through important pathways (protein disulfide isomerase, mitogen-activated protein kinases, mitochondrial function, cyclic adenosine monophosphate, Akt, and shear stress-induced platelet aggregation) with no effects on bleeding time. As a result, targeting these pathways could possibly lead to the development of helpful antiplatelet methods that usually do not improve the danger of bleeding. Keyword phrases: bioactive compounds; hemostasis; platelet; thrombosis; bleeding1. Introduction Cardiovascular disease–a top reason for morbidity and mortality among adults–is strongly influenced by platelet activation [1]. Platelets are compact and specialized diskshaped cells inside the bloodstream released from megakaryocytes and, primarily in hemostasis, can adhere and aggregate at injured vessels to arrest bleeding [2,3]. Having said that, when triggered under pathological conditions, platelet activation leads to thrombotic problems involved inside the pathogenesis of cardiovascular ailments [1,3,4]. Platelet activation and thrombus formation at atherosclerotic plaque rupture websites are dynamic processes regulated by rheological (biomechanical) and soluble-agonist-dependent mechanisms [5], although stabilization of thrombi is supported by the late wave of signaling events promoted by close speak to among aggregated platelets [6]. A case-referent study showed a significant reduction of recurrent fatal and HD1 MedChemExpress nonfatal myocardial infarction with antiplatelet drugs [7]. Presently out there antiplatelet agents, including cyclooxygenase 1 inhibitors, P2Y purinoreceptor 12 (P2Y12) antagonists, protease-activated receptor 1 antagonists, and glycoprotein (GP) IIb/IIIa antagonists, inhibit crucial processes for each thrombosis and hemostasis [8]. Therefore, current clinical research have shown that the advantage from antiplatelet therapy in key prevention is counteracted by the entailed bleeding threat [9], and also moderate bleeding was strongly connected with mortality [10]. The antiplatelet activity of a lot of fruit and vegetables and their numerous mechanisms of action have not too long ago been highlighted. Within this context, mango fruit (Mangiferaindica) [11], maqui (Aristoteliachilensis) [12], guava (Psidiumguajava) [13], tomato pomace [14], cherimoya (Annonacherimola Mill.) [15], and lupin (Lupinus spp., FabaceaePublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliat