ABSTRACT
Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) and the resulting coronavirus disease-19 (COVID-19) have led to a global pandemic associated with high fatality rates. COVID-19 primarily manifests in the respiratory system as an acute respiratory distress syndrome following viral entry through the angiotensin-converting enzyme-2 (ACE2) that is present in pulmonary epithelial cells. Central in COVID-19 is the burst of cytokines, known as a "cytokine storm", and the subsequent widespread endothelial activation, leading to cardiovascular complications such as myocarditis, arrhythmias, and adverse vascular events, among others. Genetic alterations may play an additive, detrimental role in the clinical course of patients with COVID-19, since gene alterations concerning ACE2, major histocompatibility complex class I, and toll-like receptors may predispose patients to a worse clinical outcome. Since the role of inflammation is quintessential in COVID-19, pharmacologic inhibition of various signaling pathways such as the interleukin-1 and -6, tumor necrosis factor-alpha, interferon gamma, Janus kinase-signal transducer and activator of transcription, and granulocyte-macrophage colony-stimulating factor may ameliorate the prognosis following timely administration. Finally, frequently used, non-specific anti-inflammatory agents such as corticosteroids, statins, colchicine, and macrolides represent additional therapeutic considerations.
ABSTRACT
BACKGROUND: Atherosclerotic cardiovascular diseases are characterized by a dysregulated inflammatory and thrombotic state, leading to devastating complications with increased morbidity and mortality rates. SUMMARY: In this review article, we present the available evidence regarding the impact of inflammation on platelet activation in atherosclerosis. Key messages: In the context of a dysfunctional vascular endothelium, structural alterations by means of endothelial glycocalyx thinning or functional modifications through impaired NO bioavailability and increased levels of von Willebrand factor result in platelet activation. Moreover, neutrophil-derived mediators, as well as neutrophil extracellular traps formation, have been implicated in the process of platelet activation and platelet-leukocyte aggregation. The role of pro-inflammatory cytokines is also critical since their receptors are also situated in platelets while TNF-α has also been found to induce inflammatory, metabolic, and bone marrow changes. Additionally, important progress has been made towards novel concepts of the interaction between inflammation and platelet activation, such as the toll-like receptors, myeloperoxidase, and platelet factor-4. The accumulating evidence is especially important in the era of the coronavirus disease-19 pandemic, characterized by an excessive inflammatory burden leading to thrombotic complications, partially mediated by platelet activation. Lastly, recent advances in anti-inflammatory therapies point towards an anti-thrombotic effect secondary to diminished platelet activation.
Subject(s)
Atherosclerosis/pathology , COVID-19/pathology , Inflammation Mediators/metabolism , Atherosclerosis/metabolism , COVID-19/virology , Endothelium, Vascular/metabolism , Humans , Neutrophils/metabolism , Nitric Oxide/metabolism , Platelet Activation , SARS-CoV-2/isolation & purification , von Willebrand Factor/metabolismABSTRACT
Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with excess mortality worldwide. The cardiovascular system is the second most common target of SARS-CoV-2, which leads to severe complications, including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism, as well as other major thrombotic events because of direct endothelial injury and an excessive systemic inflammatory response. This review focuses on the similarities and the differences of inflammatory pathways involved in COVID-19 and atherosclerosis. Anti-inflammatory agents and immunomodulators have recently been assessed, which may constitute rational treatments for the reduction of cardiovascular events in both COVID-19 and atherosclerotic heart disease.