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.

Lycopene Ameliorates Transplant Arteriosclerosis in Vascular Allograft Transplantation by Regulating the NO/cGMP Pathways and Rho‐Associated Kinases Expression

“…Endothelial cells are extremely important in regulating vascular tone and maintaining vascular structure [15]. However, the immune and nonimmune injuries that chronically occur in endothelial cells (ECs) may trigger endothelial activation and dysfunction in patients after organ transplantation [16].…”

Prevention and Rehabilitation After Heart Transplantation: A Clinical Consensus Statement of the European Association of Preventive Cardiology, Heart Failure Association of the ESC, and the European Cardio Thoracic Transplant Association, a Section of ESOT

“…Cardiac allograft vasculopathy is one of the leading causes of increased morbidity and mortality (which occurs in 32% of the patients at 5–10-year follow-up) in HTx recipients [ 117 , 118 ]. CAV is multifactorial and is caused by immunologic mechanisms, and stim-ulated by non-immunologic factors leading to persistent endothe-lial injury [ 119 , 120 ]. Intimal hyperplasia progresses towards coronary obstruction, which impairs perfusion up to the point of graft failure [ 118 ].…”

Role of Transient Receptor Potential Channels in Heart Transplantation: A Potential Novel Therapeutic Target for Cardiac Allograft Vasculopathy

“…The endothelium, which lines the endothelial layer of vascular trees, not only acts as a semi-permeable dynamic barrier, but is also actively involved in a variety of physiological and pathophysiological processes, such as the regulation of vascular tone, coagulation, fibrinolysis, and vascular inflammatory reactions [37,38]. TRP channels, as cellular sensors for various internal and external stimuli, participate in inflammation to mediate endothelium injury and also have crucial roles in endothelial barrier dysfunction and vascular tone regulation [39].…”