P2Y Purinoceptors as Potential Emerging Therapeutical Target in Vascular Disease

Abstract

In the last two decades a tremendous development has been noticed in our understanding of the purinergic system, consisting of heterogeneously expressed purinoceptor subtypes and its classical agonists: e.g., adenosine triphosphate, uridine triphosphate or complex dinucleoside polyphosphates. These agonists exert multiple effects on the vascular system: they regulate the relaxation and constriction of arterial blood vessels, lead to proliferation and migration in endothelial cells and vascular smooth muscle cells, and mediate potent proinflammatory responses or phenotypic cell changes. This review focuses on the P2 purinoceptor subtype P2Y and its pleiotropic effects in the vascular wall under physiological and pathophysiological condition. Various experimental and clinical studies provide evidence that pharmacological targeting of P2Y might be effective in reducing vascular alterations under disease conditions.

Purinergic Signaling and Blood Vessels in Health and Disease

“…As all cells in the vascular system express one or more types of purine receptor, this raises the possibility that purine receptors may be potential targets in vascular disease (see Schuchardt et al, 2012). Purine release mechanisms, receptors, and ectonucleotidases are all potential targets for drug development.…”

“…Reviews about the involvement of purinergic signaling in cardiovascular diseases are available (Ralevic and Burnstock, 2003;Erlinge and Burnstock, 2008;Ralevic, 2009;Burnstock and Verkhratsky, 2012;Schuchardt et al, 2012;Headrick et al, 2013). The relevance of ectonucleotidases for the treatment of cardiovascular disorders has also been reviewed (Mathieu, 2012).…”

P2X1 receptor-mediated inhibition of the proliferation of human coronary smooth muscle cells involving the transcription factor NR4A1

“…The cells also express a variety of G-protein coupled receptors for extracellular nucleotides and its breakdown product adenosine. These G-protein coupled receptors contribute to both the control of the vascular tonus by adenosine and nucleotides [5][6][7][8][9] and the control of the proliferation of the vascular smooth muscle [5,[9][10][11][12][13][14][15][16][17].…”

Role of potassium conductance in mechanisms of exrtacellular atp impact on the contractive activity of vascular smooth muscle cells

“…Пуринергические рецепторы повсемест-но ýкспрессированы на мембранах гладкомы-шечных и ýндотелиальных клеток кровеносных сосудов, что дает основание считать их патологи-ческим субстратом развития сосудистых заболе-ваний [19]. Внеклеточный АТФ, действуя на P2X-и P2Y-рецепторы кровеносных сосудов, может как стимулировать, так и ингибировать сократи-тельную активность СГМК.…”