title: Endothelial dysfunction in cardiac allograft vasculopathy: potential pharmacological interventions.
abstract: Nowadays long-term outcome of heart transplantation is limited by a peculiar type of coronary atherosclerosis, known as cardiac allograft vasculopathy (CAV). Although the exact pathogenesis of CAV remains unclear, emerging evidence indicates that the endothelium plays a significant role in the onset and progression of this disease. Nitric oxide (NO) is the principal mediator of all endothelial protective effects, due to its antinflammatory, antiproliferative, immunomodulatory and vasorelaxant properties. CAV involves immunologic mechanisms operating in the context of common cardiovascular risk factors which lead to impaired endothelial function, mainly as a consequence of decreased NO bioavailability and excessive oxidative stress. Once dysfunctional, the endothelium promotes CAV lesion progression towards the diffuse narrowing of the coronary vasculature which characterizes advanced allograft vasculopathy. Recently, many studies showed the possibility to restore endothelial dysfunction with an associated potential improvement in clinical cardiovascular outcome. Therefore, growing interest deserves the possibility to exert an endothelial protective role shown by some currently used cardiovascular and immunosuppressive drugs, as well as the future development of new pharmacological compounds with selective endothelial protective properties as a target for successful prevention and therapy of CAV.
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padova, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Osto
authors.forename: Francesco
authors.initials: F
authors.lastname: Tona
authors.forename: Emiliano
authors.initials: E
authors.lastname: De Bon
authors.forename: Sabino
authors.initials: S
authors.lastname: Iliceto
authors.forename: Guiseppe
authors.initials: G
authors.lastname: Cella
mesh_terms: D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology; D003324:Coronary Artery Disease / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D011183:Postoperative Complications / Q000503:physiopathology; D012307:Risk Factors; D014184:Transplantation, Homologous
chemical_list: D002317:Cardiovascular Agents; D007166:Immunosuppressive Agents; D009569:Nitric Oxide