Coronavirus and Cardiovascular Disease, Myocardial Injury, and Arrhythmia: JACC Focus Seminar.

The cardiovascular system is affected broadly by severe acute respiratory syndrome coronavirus 2 infection. Both direct viral infection and indirect injury resulting from inflammation, endothelial activation, and microvascular thrombosis occur in the context of coronavirus disease 2019. What determines the extent of cardiovascular injury is the amount of viral inoculum, the magnitude of the host immune response, and the presence of co-morbidities.

A2 adenosine receptors and vascular pathologies.

Cardiovascular disease, a leading cause of death and morbidity, is regulated, among various factors, by inflammation. The level of the metabolite adenosine is augmented under stress, including inflammatory, hypoxic, or injurious events. Adenosine has been shown to affect various physiological and pathological processes, largely through 1 or more of its 4 types of receptors: the A1 and A3 adenylyl cyclase inhibitory receptors and the A2A and A2B adenylyl cyclase stimulatory receptors.

Control of megakaryocyte expansion and bone marrow fibrosis by lysyl oxidase.

Lysyl oxidase (LOX), a matrix cross-linking protein, is known to be selectively expressed and to enhance a fibrotic phenotype. A recent study of ours showed that LOX oxidizes the PDGF receptor-β (PDGFR-β), leading to amplified downstream signaling. Here, we examined the expression and functions of LOX in megakaryocytes (MKs), the platelet precursors.

Adenosine and blood platelets.

Adenosine is an important regulatory metabolite and an inhibitor of platelet activation. Adenosine released from different cells or generated through the activity of cell-surface ectoenzymes exerts its effects through the binding of four different G-protein-coupled adenosine receptors. In platelets, binding of A(2) subtypes (A(2A) or A(2B)) leads to consequent elevation of intracellular cyclic adenosine monophosphate, an inhibitor of platelet activation.

Physiological implications of adenosine receptor-mediated platelet aggregation.

Adenosine is an important mediator of inhibition of platelet activation. This metabolite is released from various cells, as well as generated via activity of ecto-enzymes on the cell surface. Binding of adenosine to A(2) subtypes (A(2A) or A(2B)), G-protein coupled adenosine receptors, results in increased levels of intracellular cyclic adenosine monophosphate (cAMP), a strong inhibitor of platelet activation.