title: Extracellular nucleotide regulation and signaling in cardiac fibrosis.
abstract: Following myocardial infarction, purinergic nucleotides and nucleosides are released via non-specific and specific mechanisms in response to cellular activation, stress, or injury. These extracellular nucleotides are potent mediators of physiologic and pathologic responses, contributing to the inflammatory and fibrotic milieu within the injured myocardium. Via autocrine or paracrine signaling, cell-specific effects occur through differentially expressed purinergic receptors of the P2X, P2Y, and P1 families. Nucleotide activation of the ionotropic (ligand-gated) purine receptors (P2X) and several of the metabotropic (G-protein-coupled) purine receptors (P2Y) or adenosine activation of the P1 receptors can have profound effects on inflammatory cell function, fibroblast function, and cardiomyocyte function. Extracellular nucleotidases that hydrolyze released nucleotides regulate the magnitude and duration of purinergic signaling. While there are numerous studies on the role of the purinergic signaling pathway in cardiovascular disease, the extent to which the purinergic signaling pathway modulates cardiac fibrosis is incompletely understood. Here we provide an overview of the current understanding of how the purinergic signaling pathway modulates cardiac fibroblast function and myocardial fibrosis.
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Novitskaya
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Chepurko
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Roman
authors.initials: R
authors.lastname: Covarrubias
authors.affiliation: Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Sergey
authors.initials: S
authors.lastname: Novitskiy
authors.affiliation: Maine Medical Center, Scarborough, ME, USA.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Ryzhov
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Feoktistov
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA; Department of Pharmacology, Vanderbilt University, Nashville, TN, USA; Department of Pathology, Immunology and Microbiology, Vanderbilt University, Nashville, TN, USA. Electronic address: richard.gumina@vanderbilt.edu.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gumina
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000818:Animals; D005110:Extracellular Space / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D006868:Hydrolysis; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D009711:Nucleotides / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D009711:Nucleotides; D011983:Receptors, Purinergic; D000241:Adenosine
keywords: Adenosine; Adenosine triphosphate; Cardiac fibrosis; Ectonucleotidase; Purinergic receptors