Anti-HLA I antibodies induce VEGF production by endothelial cells, which increases proliferation and paracellular permeability

Bieri, Martin; Oroszlán, Melinda; Farkas, Anikó; Ligeti, Nathalie; Bieri, Jürg; Mohaçsi, Paul

doi:10.1016/j.biocel.2009.06.009

Cited by 31 publications

(28 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6,22,[41][42][43] In the present human study, we found that both class I and II anti-HLA antibodies were associated with allograft arteriosclerosis. The severity of arteriosclerosis was correlated with increasing circulating DSA levels and their ability to bind complement.…”

Section: Discussionsupporting

confidence: 52%

Determinants and Outcomes of Accelerated Arteriosclerosis

Loupy

Vernerey

Viglietti

et al. 2015

Circulation Research

View full text Add to dashboard Cite

Rationale: The role of circulating antibodies in addition to traditional cardiovascular risk factors in the development of accelerated arteriosclerosis and their long-term clinical consequences have not been demonstrated. Objective: We investigated the role of circulating antibodies in accelerated arteriosclerosis and the role of immune-associated arteriosclerosis in graft and patient survival and the occurrence of major adverse cardiovascular events. Methods and Results: This was an observational prospective cohort study that included 1065 kidney transplant patients (principal cohort, n=744; validation cohort, n=321) between 2004 and 2010. Participants were assessed for traditional cardiovascular risk factors and circulating anti–human leukocyte antigen (HLA) antibodies. All patients underwent allograft biopsies to assess arteriosclerotic lesions and endothelial activation, endarteritis, and complement deposition. In the principal cohort, 250 (33.6%) patients had severe arteriosclerosis (luminal narrowing >25% via fibrointimal arterial thickening). Circulating donor-specific anti-HLA antibodies were significantly associated with severe allograft arteriosclerosis (hazard ratio, 2.9; P <0.0001), independently of traditional risk factors. Patients with severe arteriosclerosis and anti-HLA antibodies (n=91, 12.2%) demonstrated allograft endothelial activation, endarteritis, and complement deposition. High levels of anti-HLA antibodies and their complement binding capacity were associated with increased severity of arteriosclerosis. Patients with antibody-associated severe arteriosclerosis had decreased allograft survival and increased mortality ( P <0.0001); they exhibited a 2.5- and 4.1-fold increased risk of major adverse cardiovascular events compared with patients who had severe arteriosclerosis without antibodies and patients with minimal arteriosclerosis, respectively ( P <0.0005). Circulating donor-specific anti-HLA antibodies were significantly associated with occurrence of major adverse cardiovascular events (hazard ratio, 2.4; P =0.0004), independently of traditional risk factors. Conclusions: Circulating antibodies are major determinants of severe arteriosclerosis and major adverse cardiovascular events, independent of traditional cardiovascular risk factors.

show abstract

Section: Discussionsupporting

confidence: 52%

Determinants and Outcomes of Accelerated Arteriosclerosis

Loupy

Vernerey

Viglietti

et al. 2015

Circulation Research

View full text Add to dashboard Cite

show abstract

“…It has been shown that ligation of anti-class I antibodies to class I molecules on the vascular endothelium and smooth muscle cells inducesreleaseofavarietyofcytokinesandstimulatesproliferationof myofibroblasts. [10][11][12][13] Similar reactions occur with anti-class II anti- . CLINICAL RESEARCH www.jasn.org bodies, and evidence would suggest that these antibodies correlate better with both morphologic and functional changes than do class I antibodies.…”

Section: Role Of Dsa Positivitymentioning

confidence: 99%

Donor-Specific Antibodies Accelerate Arteriosclerosis after Kidney Transplantation

Hill

Nochy²,

Bruneval³

et al. 2011

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

In biopsies of renal allografts, arteriosclerosis is often more severe than expected based on the age of the donor, even without a history of rejection vasculitis. To determine whether preformed donor-specific antibodies (DSAs) may contribute to the severity of arteriosclerosis, we examined protocol biopsies from patients with (n ϭ 40) or without (n ϭ 59) DSA after excluding those with any evidence of vasculitis. Among DSA-positive patients, arteriosclerosis significantly progressed between month 3 and month 12 after transplant (mean Banff cv score 0.65 Ϯ 0.11 to 1.12 Ϯ 0.10, P ϭ 0.014); in contrast, among DSA-negative patients, we did not detect a statistically significant progression during the same timeframe (mean Banff cv score 0.65 Ϯ 0.11 to 0.81 Ϯ 0.10, P ϭ not significant). Available biopsies at later time points supported a rate of progression of arteriosclerosis in DSA-negative patients that was approximately one third that in DSA-positive patients. Accelerated arteriosclerosis was significantly associated with peritubular capillary leukocytic infiltration, glomerulitis, subclinical antibody-mediated rejection, and interstitial inflammation. In conclusion, these data support the hypothesis that donorspecific antibodies dramatically accelerate post-transplant progression of arteriosclerosis.

show abstract

“…Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis that induces the formation of novel blood vessels, and the growth and metastasis of cancers (7,8). The growth and spread of tumors depends on the formation of an adequate vascular support and amoeboid mode of tumor cell invasion (9).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-126 affects ovarian cancer cell differentiation and invasion by modulating expression of vascular endothelial growth factor

et al. 2018

View full text Add to dashboard Cite

Abstract. Primary ovarian cancer is the main cause of gynecological cancer-associated mortality. However, the mechanism behind the spread of ovarian cancer requires elucidation. The present study aimed to investigate the effects of microRNA-126 (miR-126) on differentiation and invasion, and its mechanism in primary ovarian cancer. Ovarian cancer SKOV3 cells transfected with LV3-has-miR-126 mimics and LV3-has-miR-126 inhibitor were produced; it was revealedthatLV-miR-126 mimics could induce cell cycle arrest at G 1 phase, suppress cell invasion through Matrigel-coated membranes and downregulate the expression of vascular endothelial growth factor (VEGF). Furthermore, LV-has-miR-126 inhibitor-transfected cells could increase the number of cells in S phase, induce cell invasion and upregulate the expression of VEGF. The present study, to the best of our knowledge, is the first to report that miR-126 may serve tumor suppressor roles by inducing G 1 cell cycle arrest and suppressing invasion in ovarian cancer cells, at least in part by targeting VEGF expression.

show abstract

Anti-HLA I antibodies induce VEGF production by endothelial cells, which increases proliferation and paracellular permeability

Cited by 31 publications

References 30 publications

Determinants and Outcomes of Accelerated Arteriosclerosis

Determinants and Outcomes of Accelerated Arteriosclerosis

Donor-Specific Antibodies Accelerate Arteriosclerosis after Kidney Transplantation

MicroRNA-126 affects ovarian cancer cell differentiation and invasion by modulating expression of vascular endothelial growth factor

Contact Info

Product

Resources

About