Inhibition of vascular endothelial growth factor reduces cardiac allograft vasculopathy

Chatur, Safia; Wong, Brian W.; Carthy, Jon M.; McManus, Bruce M.

doi:10.1016/j.healun.2016.04.011

Cited by 10 publications

(7 citation statements)

References 34 publications

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“…Endothelial injury and repair have previously been implicated in the pathogenesis of CAV. In a mouse model, vascular endothelial growth factor (VEGF) inhibition was shown to reduce severity and incidence of CAV, while attenuating myocardial edema and neo‐angiogenesis 53 . Daly et al found vascular endothelial growth factor (VEGF)‐C, VEGF‐A, and platelet factor‐4 (PF‐4) as significant independent biomarkers of angiographically documented CAV (area under the curve [AUC] = 0.98; p < .001) 14 .…”

Section: Discussionmentioning

confidence: 99%

Donor‐derived cell‐free DNA is associated with cardiac allograft vasculopathy

Holzhauser

Clerkin

Fujino

et al. 2021

Clinical Transplantation

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Background The role of donor‐derived cell‐free DNA (dd‐cfDNA) in screening for cardiac allograft vasculopathy (CAV) is unknown. We hypothesized that dd‐cfDNA correlates with CAV, markers of inflammation, and angiogenesis in stable heart transplant (HT) recipients. Methods Sixty‐five HT recipients ≥2 years post‐transplant, without recent rejection, were stratified by high (≥0.12%) versus low levels (<0.12%) of dd‐cfDNA. A targeted amplification, next‐generation sequencing assay (AlloSure®; CareDx, Inc.) was used to detect dd‐cfDNA. Peripheral blood inflammatory and angiogenesis markers were assessed using a multiplex immunoassay system (Bioplex®). Results Of 65 patients, 58 patients had a known CAV status and were included. Thirty had high levels of dd‐cfDNA (≥0.12%), and 28 had low levels (<0.12%). CAV was present in 63% of patients with high dd‐cfDNA vs. 35% with low dd‐cfDNA (p = .047). Donor‐specific antibodies were present in 25% of patients with high dd‐cfDNA vs. 3.8% in those with low dd‐cfDNA (p = .03). There were no differences in rejection episodes, inflammatory, or angiogenesis markers. Importantly, dd‐cfDNA levels were not different when stratified by time post‐transplant. Conclusions Higher dd‐cfDNA levels were associated with CAV in stable chronic HT recipients. Further studies are warranted to investigate a possible association between dd‐cfDNA levels and CAV severity and whether dd‐cfDNA can predict CAV progression.

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Section: Discussionmentioning

confidence: 99%

Donor‐derived cell‐free DNA is associated with cardiac allograft vasculopathy

Holzhauser

Clerkin

Fujino

et al. 2021

Clinical Transplantation

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“…Studies that have demonstrated incremental benefits in terms of preventing or slowing the progression of CAV have been conducted on rodent models. 24-27 This pilot study evaluated the efficacy of a CXCR4 antagonist combined with CNI-free ISDs for controlling both acute rejection and CAV in a swine model of allogeneic heterotopic cardiac transplantation. A favorable survival trend was observed in the burixafor 2D group, and a significantly prolonged graft survival was achieved through intensified treatment in the burixafor 2D + B group.…”

Section: Discussionmentioning

confidence: 99%

CXCR4 Antagonist Reduced the Incidence of Acute Rejection and Controlled Cardiac Allograft Vasculopathy in a Swine Heart Transplant Model Receiving a Mycophenolate-based Immunosuppressive Regimen

et al. 2018

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“…Last, VEGF is elevated in numerous other pathologic conditions, and the relationship between VEGF and post-transplant lymphoproliferative disorder or other potential comorbidities remains unknown. The described association between elevated serum VEGF concentration and development of CAV is part of a growing body of literature demonstrating that VEGF is an important contributor in the pathogenesis of CAV 2,19 and could have potential as a clinically relevant biomarker in pediatric heart transplant recipients.…”

Section: Limitationsmentioning

confidence: 99%

“…2 In a murine model of CAV in heterotopically transplanted hearts, treatment with a VEGF inhibitor (soluble VEGF receptor 1) reduced the severity and incidence of CAV. 19 …”

mentioning

confidence: 99%

Elevated serum vascular endothelial growth factor and development of cardiac allograft vasculopathy in children

Watanabe

Karimpour-Fard

Michael

et al. 2018

The Journal of Heart and Lung Transplantation

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BACKGROUND: Cardiac allograft vasculopathy (CAV) is a leading cause of retransplantation and death in pediatric heart transplant recipients. Our aim was to evaluate the association between serum vascular endothelial growth factor-A (VEGF) and CAV development in the pediatric heart transplant population. METHODS: In this retrospective study performed at a university hospital, VEGF concentrations were measured by enzyme-linked immunosorbent assay in banked serum from pediatric heart transplant recipients undergoing routine cardiac catheterization. In subjects with CAV (n = 29), samples were obtained at 2 time-points: before CAV diagnosis (pre-CAV) and at the time of initial CAV diagnosis (CAV). In subjects without CAV (no-CAV, n = 16), only 1 time-point was used. VEGF concentrations (n = 74) were assayed in duplicate. RESULTS: Serum VEGF is elevated in pediatric heart transplant recipients before catheter-based diagnosis of CAV (no-CAV mean: 144.0 ± 89.05 pg/ml; pre-CAV mean: 316.2 ± 118.3 pg/ml; p = 0.0002). Receiver-operating characteristic curve analysis of pre-CAV VEGF levels demonstrated an area under the curve of 87.7% (p = 0.0002), with a VEGF level of 226.3 pg/ml predicting CAV development with 77.8% sensitivity and 91.7% specificity. VEGF is similarly elevated in subjects with angiographically diagnosed CAV and in those with normal angiography but intravascular ultrasound (IVUS) evidence of CAV. CONCLUSIONS: The increase in serum VEGF before onset of detectable CAV is fundamental to its utility as a predictive biomarker and suggests further investigations of VEGF in the pathogenesis of CAV are warranted in the pediatric heart transplant population.

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Inhibition of vascular endothelial growth factor reduces cardiac allograft vasculopathy

Cited by 10 publications

References 34 publications

Donor‐derived cell‐free DNA is associated with cardiac allograft vasculopathy

Donor‐derived cell‐free DNA is associated with cardiac allograft vasculopathy

CXCR4 Antagonist Reduced the Incidence of Acute Rejection and Controlled Cardiac Allograft Vasculopathy in a Swine Heart Transplant Model Receiving a Mycophenolate-based Immunosuppressive Regimen

Elevated serum vascular endothelial growth factor and development of cardiac allograft vasculopathy in children

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