However, in certain conditions associated with high levels of angiotensin II, TF expression is evident also in endothelial cells [33]

However, in certain conditions associated with high levels of angiotensin II, TF expression is evident also in endothelial cells [33]. acute respiratory syndrome (SARS) caused by a novel coronavirus (SARS-CoV-2), was described in consecutive cases in Wuhan, China, and later defined by the World Health Organization (WHO) as coronavirus disease 2019 (COVID-19) pandemic, following a rapid worldwide spread. It is well established that SARS-CoV-2 causes multiple serious complications, where the most prominent are severe acute respiratory distress syndrome (ARDS) as well as L-(-)-α-Methyldopa (hydrate) multiple organ dysfunction including heart and kidney failure and coagulopathy [1C4]. While the deleterious impact of SARS-CoV-2 on pulmonary, cardiac and renal systems has been studied extensively, the adverse effects of this virus on coagulation process is still L-(-)-α-Methyldopa (hydrate) underestimated. COVID-19 and coagulation Patients with COVID-19 exhibit clotting disorders that adversely affect the prognosis of the disease, and result in higher mortality rates [5C7]. Numerous studies have shown that abnormal coagulation markers, particularly markedly elevated d-dimer, fibrin degradation product (FDP), prolonged prothrombin time, and thrombocytopenia are common in severe patients or non-survivors of COVID-19 [8,9]. Indeed, patients infected by this novel coronavirus are at higher risk for overt disseminated intravascular coagulation (DIC) [1,8,10]. The pathogenesis of hypercoagulability in COVID-19 is not completely understood. However, excessive systemic inflammatory process, platelet activation, blood stasis in immobilized patients, and endothelial dysfunction are among possible etiologic factors that may induce coagulation abnormalities in COVID-19 patients [11C15]. Recent studies (some are observational) had documented lower mortality rate in COVID-19 patients who received anticoagulants in different regimens and dosesboth prophylactic and treatment [16]. Similar dysregulations of coagulation system manifested in other coronavirus infections, such as Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-1) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) [17], suggesting a common downstream pathway underlying COVID-19-induced serious coagulation complication. Unfortunately, the mechanisms responsible for this phenomenon are poorly characterized. One of the potential systems that may play a crucial role in the exaggerated coagulation characterizing COVID-19 is the Heparan sulfate proteoglycan (HSPG) and Heparanase system. In this commentary, we will refer to potential evidences about the involvement of HSPGs and heparanase in COVID-19-induced coagulopathy, infectivity of SARS-CoV-2 and viral cell release. HSPGs and heparanase HSPGs are ubiquitous constituents of the cell surface and the extracellular matrix (ECM). These macromolecules are largely responsible for binding various proteins, hormones, cytokines, and growth factors to their binding sites on the cell surface, where they exert cardinal functions related to cellCECM interactions [18C20]. Heparanase, an endo–d-glucuronidase, is the only enzyme in mammals that degrades heparan sulfate (HS) chains of HSPGs [21C24]. Heparanase is involved in a wide variety of pathological processes and diseases, where elevated levels of heparanase were demonstrated, including inflammatory and infectious processes [25,26]. In addition, higher heparanase levels were measured in several malignancies [27C30], where the higher abundance of heparanase was associated with more aggressive and advanced disease, besides the occurrence of more disease-related complications [31]. Heparanase and coagulation Tissue factor (TF), a transmembrane protein, is the main cellular initiator of blood coagulation, where it is expressed in most body cells except blood and endothelial cells. However, in certain conditions associated with high levels of angiotensin II, TF expression is evident also in endothelial cells [33]. TF functions as a receptor and cofactor of plasma factor VII, where together they activate factor X and subsequently the coagulation cascade upon disturbance of vascular integrity [34]. TF pathway inhibitor (TFPI), a multivalent Kunitz-type plasma proteinase inhibitor, is the only endogenous modulator of TF, and is localized to cell surface.TF functions as a receptor and cofactor of plasma factor VII, where together they activate factor X and subsequently the coagulation cascade upon disturbance of vascular integrity [34]. could be blocked by heparanase inhibitors such as Heparin and Pixatimod. strong class=”kwd-title” Keywords: Coagulopathy, COVID-19, Heparanase, SARS-COV-2 Background In December 2019, a severe acute respiratory syndrome (SARS) caused by a novel coronavirus (SARS-CoV-2), was described in consecutive cases in Wuhan, China, and later defined by the World Health Organization (WHO) as coronavirus disease 2019 (COVID-19) pandemic, following a rapid worldwide spread. It is well established that SARS-CoV-2 causes multiple serious complications, where the most prominent are severe acute respiratory distress syndrome (ARDS) as well as multiple organ dysfunction including heart and kidney failure and coagulopathy [1C4]. While the deleterious impact of SARS-CoV-2 on pulmonary, cardiac and renal systems has been studied extensively, the adverse effects of this virus on coagulation process is still underestimated. COVID-19 and coagulation Patients with COVID-19 exhibit clotting disorders that adversely affect the prognosis of the disease, and result in higher mortality rates [5C7]. Numerous studies have shown that abnormal coagulation markers, particularly markedly elevated d-dimer, fibrin degradation product (FDP), prolonged prothrombin time, and thrombocytopenia are common in severe patients or non-survivors of COVID-19 [8,9]. Indeed, patients infected by this novel coronavirus are at higher risk for overt disseminated intravascular coagulation (DIC) [1,8,10]. The pathogenesis of hypercoagulability in COVID-19 is not completely understood. However, excessive systemic inflammatory process, platelet activation, blood stasis in immobilized patients, and endothelial dysfunction are among possible etiologic factors that may induce coagulation abnormalities in COVID-19 patients [11C15]. Recent studies (some are observational) had documented lower mortality rate in COVID-19 patients who received anticoagulants in different regimens and dosesboth prophylactic and treatment [16]. Similar dysregulations of coagulation system manifested in other coronavirus infections, such as Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-1) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) [17], suggesting a common downstream pathway underlying COVID-19-induced serious coagulation complication. Unfortunately, the mechanisms responsible for this phenomenon are poorly characterized. One of the potential systems that may play a crucial role in the exaggerated coagulation characterizing COVID-19 is the Heparan sulfate proteoglycan (HSPG) and Heparanase system. In this commentary, we will refer to potential evidences about the involvement of HSPGs and heparanase in COVID-19-induced coagulopathy, infectivity of SARS-CoV-2 and viral cell release. HSPGs and heparanase HSPGs are ubiquitous constituents of the cell surface and the extracellular matrix (ECM). These macromolecules are L-(-)-α-Methyldopa (hydrate) L-(-)-α-Methyldopa (hydrate) largely responsible for binding various proteins, hormones, cytokines, and growth factors to their binding sites on the cell surface, where they exert cardinal functions related to cellCECM interactions [18C20]. Heparanase, an endo–d-glucuronidase, is the only enzyme in mammals that degrades heparan sulfate (HS) chains of HSPGs [21C24]. Heparanase is involved in a wide variety of pathological processes and diseases, where elevated levels of heparanase were demonstrated, including inflammatory and infectious Rabbit Polyclonal to OR2T10 processes [25,26]. In addition, higher heparanase levels were measured in several malignancies [27C30], where the higher abundance of heparanase was associated with more aggressive and advanced disease, besides the occurrence of more disease-related complications [31]. Heparanase and coagulation Tissue factor (TF), a transmembrane protein, is the main cellular initiator of blood coagulation, where it is expressed in most body cells except blood and endothelial cells. However, in certain conditions associated with high levels of angiotensin II, TF expression is evident also in endothelial cells [33]. TF functions as a receptor and cofactor of plasma factor VII, where together they activate factor X and subsequently the coagulation cascade upon disturbance of vascular integrity [34]. TF pathway inhibitor (TFPI), a multivalent Kunitz-type plasma proteinase inhibitor, is the only endogenous modulator of.