Cardiac allograft vasculopathy

Abstract

Cardiac transplantation has emerged as a valuable therapy for various end-stage cardiac disorders. Cardiac allograft vasculopathy (CAV), an unusually accelerated and diffuse form of obliterative coronary arteriosclerosis, determines long-term function of the transplanted heart. Cardiac allograft vasculopathy is a complicated interplay between immunologic and nonimmunologic factors resulting in repetitive vascular injury and a localized sustained inflammatory response. Dyslipidemia, oxidant stress, immunosuppressive drugs, and viral infection appear to be important contributors to disease development. Endothelial dysfunction is an early feature of CAV and progresses over time after transplantation. Early identification of CAV is essential if long-term prognosis is to be improved. Annual coronary angiography is performed for diagnostic and surveillance purposes. Intravascular ultrasound is a more sensitive diagnostic tool for early disease stages and has revealed that progressive luminal narrowing in CAV is in part due to negative vascular remodeling. Because of the diffuse nature of CAV, percutaneous and surgical revascularization procedures have a limited role. Prevention of CAV progression is a primary therapeutic goal.

The Universal NF-kappaB Inhibitor A20 Protects From Transplant Vasculopathy by Differentially Affecting Apoptosis in Endothelial and Smooth Muscle Cells

“…Late graft failure is secondary to chronic rejection, characterized by the development of a pathognomonic occlusive vasculopathy, termed transplant-vasculopathy (TV). TV is particularly dramatic in cardiac transplant recipients and has become the principle cause of late death and allograft dysfunction (3). Pathologically, with the exception of foam cell development, occlusive lesions of TV closely resemble that of atherosclerotic plaques.…”

Effects of Immunosuppressive agents on neutrophils inflammatory response in humans: An inflammatory perspective on coronary allograft vasculopathy

“…Macrophages are then recruited to the intima where they release cytokines (IL-1; IL-6; TNF-alpha) and growth factors (platelet derived growth factors (PDGF), transforming growth factor-alpha (TGF-alpha), and TGF-beta1), inducing SMC proliferation and synthesis of extracellular matrix [16] . T cells activation also stimulates the expression of adhesion molecules (intercellular cell adhesion molecule -1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-selectin thereby activating endothelial cells, enabling recruitment of neutrophils and the development of CAV [11,[17][18][19][20][21][22][23] . Indeed most pro-inflammatory markers are elevated early and late following CTx [3,24] .…”

Pathologic diagnosis of antibody-mediated rejection in endomyocardial biopsy after heart transplantation based on renewed International Society for Heart and Lung Transplantation criteria

“…This mechanism explains why AMR in heart EMB is usually referred to coronary allograft vasculopathy (CAV) and manifests as diffuse atherosclerosis with myointimal proliferation in the coronary arteries [9,11]. It was estimated that about 50% of heart transplant recipients have angiographically confirmed CAV by 5 years after transplantation, and severe CAV is a major cause of death in patients surviving the first post-transplantation year [18,19]. Other studies [20,21] suggested that cytokines/chemokines such as interleukin (IL)-1-α, IL-8, RANTES and monocyte chemotactic protein 1 (MCP-1) are upregulated in rejected hearts.…”