Allograft Arteriosclerosis and Immune-Driven Angiogenesis

Libby, Peter; Zhao, David

doi:10.1161/01.cir.0000059744.64373.08

Cited by 33 publications

(16 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In chronic inflammation, where tissue destruction and mononuclear cell infiltration are dominant, the persistent delivery and local expression of angiogenesis factors can serve to sustain the angiogenesis response (33)(34)(35)(36)(37)(38). In its normal guise, angiogenesis is thought to facilitate the repair of injured tissues and to restore oxygenation.…”

Section: Discussionmentioning

confidence: 99%

Molecular Pathways Involved in Loss of Kidney Graft Function with Tubular Atrophy and Interstitial Fibrosis

Maluf

Mas

Archer

et al. 2008

Mol Med

View full text Add to dashboard Cite

Loss of kidney graft function with tubular atrophy (TA) and interstitial fibrosis (IF) causes most kidney allograft losses. We aimed to identify the molecular pathways involved in IF/TA progression. Kidney biopsies from normal kidneys (n = 24), normal allografts (n = 6), and allografts with IF/TA (n = 17) were analyzed using high-density oligonucleotide microarray. Probe set level tests of hypotheses tests were conducted to identify genes with a significant trend in gene expression across the three groups using Jonckheere-Terpstra test for trend. Interaction networks and functional analysis were used. An unsupervised hierarchical clustering analysis showed that all the IF/TA samples were associated with high correlation. Gene ontology classified the differentially expressed genes as related to immune response, inflammation, and matrix deposition. Chemokines (CX), CX receptor (for example, CCL5 and CXCR4), interleukin, and interleukin receptor (for example, IL-8 and IL10RA) genes were overexpressed in IF/TA samples compared with normal allografts and normal kidneys. Genes involved in apoptosis (for example, CASP4 and CASP5) were importantly overexpressed in IF/TA. Genes related to angiogenesis (for example, ANGPTL3, ANGPT2, and VEGF) were downregulated in IF/TA. Genes related to matrix production-deposition were upregulated in IF/TA. A distinctive gene expression pattern was observed in IF/TA samples compared with normal allografts and normal kidneys. We were able to establish a trend in gene expression for genes involved in different pathways among the studied groups. The top-scored networks were related to immune response, inflammation, and cellto-cell interaction, showing the importance of chronic inflammation in progressive graft deterioration.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular Pathways Involved in Loss of Kidney Graft Function with Tubular Atrophy and Interstitial Fibrosis

Maluf

Mas

Archer

et al. 2008

Mol Med

View full text Add to dashboard Cite

show abstract

“…A ngiogenesis is well established to be a characteristic component of immune inflammation and has been shown to be of pathologic significance in ischemic and chronic inflammatory diseases, including diabetes, retinopathy, atherosclerosis, allograft rejection, coronary artery disease, and myocardial infarction (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Moreover, several acute and chronic renal diseases, including ischemic nephropathy, glomerulonephritis, and interstitial nephritis, were found recently to be associated with angiogenesis, and there is interest in the concept that manipulation of this response can attenuate the disease process (9,14 -19).…”

mentioning

confidence: 99%

“…In this circumstance, the resolution of the acute response coincides with a resolution of the healing angiogenesis response. In contrast, in chronic inflammation, in which tissue destruction and mononuclear cell infiltration are dominant, the persistent delivery and local expression of angiogenesis factors can serve to sustain the angiogenesis response (4,12,(23)(24)(25)(26). In its normal guise, angiogenesis is thought to facilitate the repair of injured tissues and to restore oxygenation.…”

mentioning

confidence: 99%

Angiogenesis and Endothelial Cell Repair in Renal Disease and Allograft Rejection

Reinders

Rabelink

Briscoe

2006

Journal of the American Society of Nephrology

134

144

View full text Add to dashboard Cite

show abstract

“…2,[11][12][13][14][15][16] Animal models are limited by the fact that they do not recapitulate the human pathophysiology of immune-mediated vascular injury, [17][18][19] whereas human studies lack access to patient arteries for histopathologic analysis and exhibit slow disease progression. As a consequence, we have an incomplete understanding of the respective contributions of nonimmune and immune factors in arteriosclerosis and their local (organ failure) and more general consequences (patient death and cardiovascular events).…”

mentioning

confidence: 99%

“…In view of the profound interactions between the immune system and the vessels that characterize solid organ transplantation, 2,[20][21][22][23][24][25] we used a population-based approach to assess the determinants of premature arteriosclerosis in a cohort of extensively phenotyped kidney transplant patients. Although observations have suggested an association between antibodies and local allograft arteriosclerosis, 5,26 the extent to which antibodies are independent risk factors in premature arteriosclerosis and occurrence of major cardiovascular events (MACE), beyond traditional risk factors, is still unknown.…”

mentioning

confidence: 99%

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

Allograft Arteriosclerosis and Immune-Driven Angiogenesis

Cited by 33 publications

References 17 publications

Molecular Pathways Involved in Loss of Kidney Graft Function with Tubular Atrophy and Interstitial Fibrosis

Molecular Pathways Involved in Loss of Kidney Graft Function with Tubular Atrophy and Interstitial Fibrosis

Angiogenesis and Endothelial Cell Repair in Renal Disease and Allograft Rejection

Determinants and Outcomes of Accelerated Arteriosclerosis

Contact Info

Product

Resources

About