The challenge of allograft vasculopathy in cardiac transplantation

Arora, Satish; Gullestad, Lars

doi:10.1097/mot.0000000000000112

Cited by 16 publications

(16 citation statements)

References 42 publications

(35 reference statements)

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“…The immunobiology of vasculopathy has been studied in great detail in cardiac transplantation . The term is sometimes used interchangeably with chronic rejection, but evidence suggests vasculopathy is more complex than an incompletely controlled rejection response, although suboptimal immunosuppression has been shown to induce vasculopathy in animal models .…”

Section: Tissue Components Of Composite Allograftsmentioning

confidence: 99%

Immunobiology in VCA

et al. 2016

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SUMMARYTransplantation of vascularized composite tissue is a relatively new field that is an amalgamation of experience in solid organ transplantation and reconstructive plastic and orthopedic surgery. What is novel about the immunobiology of VCA is the addition of tissues with unique immunologic characteristics such as skin and vascularized bone, and the nature of VCA grafts, with direct exposure to the environment, and external forces of trauma. VCAs are distinguished from solid organ transplants by the requirement of rigorous physical therapy for optimal outcomes and the fact that these procedures are not lifesaving in most cases. In this review, we will discuss the immunobiology of these systems and how the interplay can result in pathology unique to VCA as well as provide potential targets for therapy.

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Section: Tissue Components Of Composite Allograftsmentioning

confidence: 99%

Immunobiology in VCA

et al. 2016

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“…These data support that adventitial macrophages may enhance mural cell miR-21 expression via a paracrine mechanism. Given the pivotal role of proliferation and migration of medial SMCs in the development of transplant vasculopathy [3–5, 7], and the well documented detrimental effects of miR-21 in pathological vascular remodeling [19, 27, 29, 30, 37, 38], we suggest that the observed beneficial effects of macrophage depletion in aortic allografts are, at least in part, due to reduced miR-21 expression in vascular mural cells.…”

Section: Discussionmentioning

confidence: 87%

“…For example, population studies have suggested that around 90% of patients receiving heart transplantation will develop transplant vasculopathy within 10 years [6]. Transplant vasculopathy is also known as transplant arteriosclerosis, which is characterized by progressing neointimal hyperplasia, luminal stenosis, and finally ischemic graft failure [3–5]. …”

Section: Introductionmentioning

confidence: 99%

“…It has been recognized that proliferation and migration of vascular smooth muscle cells (VSMCs) driven by multiple local and systemic factors have a pivotal role in transplant vasculopathy [3–5, 7]. Although these processes are also involved in the pathogenesis of angioplasty-induced restenosis, there are fundamental differences between these two diseases.…”

Section: Introductionmentioning

confidence: 99%

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Macrophage-stimulated microRNA expression in mural cells promotes transplantation-induced neointima formation

et al. 2017

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In this study, we tested the possibility that macrophages might contribute to neointima formation by stimulating microRNA expressions in mural cells. Thoracic aortas from F344 rats were transplanted into recipient Lewis rats. Clodronate liposome was used for in vivo macrophage depletion. Using miR-21 as a prototypic example of vascular enriched microRNA, we showed that macrophage depletion reduced the expression level of miR-21, which was upregulated in the allograft. This effect of macrophage depletion was accompanied by attenuations in neointimal hyperplasia and transplantation-induced vascular inflammation. Using in vitro assays, we identified that macrophages might stimulate miR-21 expression in smooth muscle cells and adventitial fibroblasts via the release of tumor necrosis factor-α. We also showed that silencing of miR-21 suppressed tumor necrosis factor-induced proliferation, migration, and inflammatory responses in mural cells. Our results suggest that macrophage may promote transplantation-induced neointima formation by stimulating miR-21 expression in vascular mural cells, which promotes mural cell proliferation, migration and/or inflammation. Moreover, we have established that tumor necrosis factor-α has a major role in mediating this paracrine process.

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“…This results in abnormal cell proliferation and protein synthesis via the activation of p70 ribosomal S6 kinase and eukaryotic initiation factor 4E‐binding protein . Cytokines released by activated T‐lymphocytes also activate donor endothelial cells and promote expression of adhesion molecules (intercellular adhesion molecule‐1, vascular adhesion molecule‐1, and P‐selectin), which mediate further recruitment and accumulation of T‐lymphocytes and macrophages in the vessel intima, leading to a sustained inflammatory response . Macrophages secrete cytokines and growth factors that further stimulate the proliferation and migration of coronary smooth muscle cells to promote abnormal intimal thickening and extracellular matrix deposition .…”

Section: Pathogenesismentioning

confidence: 99%

Cardiac allograft vasculopathy: Insights on pathogenesis and therapy

Lee

Nair

Chih

2020

Clinical Transplantation

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Cardiac allograft vasculopathy (CAV) is a unique accelerated form of coronary vascular disease affecting heart transplant recipients. This complication is a significant contributor to medium‐ to long‐term post‐transplant morbidity and mortality. There is a high prevalence of CAV with approximately one in three patients developing CAV by 5 years post‐transplant. Morphologically, CAV is characterized by concentric coronary intimal hyperplasia in both the epicardial arteries and intramural microvasculature. Although several immune and non‐immune factors have been identified, their precise pathogenic mechanisms, interactions, and relative importance in the development of CAV are not well defined. The advent of improved imaging surveillance modalities has resulted in earlier detection during the disease process. However, overall management of CAV remains challenging due to paucity of treatment. This review aims to discuss key concepts on the pathogenesis of CAV and current management strategies, focusing on the use of mammalian target of rapamycin inhibitors.

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The challenge of allograft vasculopathy in cardiac transplantation

Cited by 16 publications

References 42 publications

Immunobiology in VCA

Immunobiology in VCA

Macrophage-stimulated microRNA expression in mural cells promotes transplantation-induced neointima formation

Cardiac allograft vasculopathy: Insights on pathogenesis and therapy

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