Endothelial Dysfunction and Cardiac Allograft Vasculopathy

Abstract

Cardiac allograft vasculopathy remains a major challenge to long-term survival after heart transplantation. Endothelial injury and dysfunction, as a result of multifactorial immunologic and nonimmunologic insults in the donor and the recipient, are prevalent early after transplant and may be precursors to overt cardiac allograft vasculopathy. Current strategies for managing cardiac allograft vasculopathy, however, rely on the identification and treatment of established disease. Improved understanding of mechanisms leading to endothelial dysfunction in heart transplant recipients may provide the foundation for the development of sensitive screening techniques and preventive therapies.

Cardiac Allograft Vasculopathy: A Review of Risk Factors and Pathogenesis

“…Endothelial injury and dysfunction leads to imbalance between endothelial derived relaxing factors (EDRFs) and endothelium-derived constricting factors (EDCFs). EDCFs promote inflammation and contribute to the development of atherosclerosis by attenuating the action of EDRFs [2,8,27,29,[45][46][47][48][49][50][51][52][53].…”

“…CAV is multifactorial in origin and is considered to be a form of chronic rejection previously due to the crucial role played by various alloimmune and autoimmune mechanisms in the pathogenesis of CAV [6][7][8]. Although immune mediated factors play a major role, several studies have demonstrated the role of traditional risk factors of coronary artery disease (CAD) in the progression of CAV [8][9][10].…”

“…Although immune mediated factors play a major role, several studies have demonstrated the role of traditional risk factors of coronary artery disease (CAD) in the progression of CAV [8][9][10]. Based on progress gained in this field, CAV is currently viewed as an "impaired response to vascular injury" resulting in altered permeability, migration of smooth muscle cells and fibroproliferation [10].…”

“…Based on progress gained in this field, CAV is currently viewed as an "impaired response to vascular injury" resulting in altered permeability, migration of smooth muscle cells and fibroproliferation [10]. This results in diffuse concentric hypertrophy of the vessel wall and microvascular occlusion leading to pathologic remodeling of the transplant heart vasculature [8]. It affects epicardial, intramural arteries, and veins and causes diffuse luminal narrowing which could lead to myocardial infarction (MI) and graft dysfunction [11].…”

Characteristics of Cardiac Allograft Vasculopathy Induced by Immunomodulation in the Miniature Swine

“…[1][2][3][4][5][6][7] It is suggested that CAV development begins as a "response to injury," initial endothelial dysfunction followed by intimal hyperplasia as a result of vascular remodeling in response to initial reperfusion injury and repetitive immunological transplant-related endothelial injury. 2) These vascular remodeling and smooth muscle cell (SMC) proliferation are potentiated by inflammatory cytokines, growth factors, and chemotactic factors produced by activated endothelial cells and migrating cells, resulting in the activation of SMC and their migration from the media to the intima. 7) Activated SMC further proliferate and secrete cytokines, which potentiate proliferation and subsequent matrix deposition and luminal narrowing.…”