Impaired angiogenesis in the aging kidney: Vascular endothelial growth factor and Thrombospondin-1 in renal disease

Kang, Duk Hee; Anderson, Sharon; Kim, Yoon Goo; Mazzalli, Marilda; Suga, Shin Ichi; Jefferson, J. Ashley; Gordon, Katherine; Oyama, T; Hughes, Jeremy; Hugo, Christian; Kerjaschki, D; Schreiner, George F.; Johnson, Richard J.

doi:10.1053/ajkd.2001.22087

Cited by 306 publications

(282 citation statements)

References 37 publications

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“…The loss of capillaries is correlated with the loss of VEGF in the kidney, conditions that favor endothelial cell loss and impaired angiogenesis. 56 VEGF treatment reduced fibrosis and stabilized renal function in the remnant kidney model. 57 Administration of VEGF also restored the number of peritubular capillaries and protected the kidney in our thrombotic microangiopathy model.…”

Section: Another Final Common Pathway Chronic Hypoxiamentioning

confidence: 87%

Final common pathways of progression of renal diseases

Nangaku

2002

Clinical and Experimental Nephrology

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Complement activation plays a critical role in the pathogenesis of many forms of glomerulonephritis. Studies utilizing cultured glomerular cells and animal models have clarified the important role of imbalance between complement activation and complement regulatory proteins in the pathogenesis of immune-mediated glomerular injury. Glomerular injury results not only from glomerulonephritis but occurs through a variety of mechanisms, including those associated with hypertension and diabetes mellitus. However, once glomerular damage reaches a certain threshold, progression of renal disease is consistent and irreversible. Pathological studies have revealed a close correlation between tubulointerstitial damage and poor prognosis, emphasizing the crucial role of tubulointerstitial injury in eventual kidney failure. One common mechanism that leads to renal failure via tubulointerstitial injury is massive proteinuria. Specific components of the filtered protein may be toxic to tubular cells. Among various harmful proteins filtered through the glomerular barrier are complement components, which are activated by ammonium resulting from excess delivery of protein to tubular cells. Another common mechanism is chronic ischemia in the tubulointerstitium. Tubulointerstitial damage results in the loss of peritubular capillaries and induces chronic hypoxia in this compartment, producing a vicious cycle. Therapeutic approaches that target these final common pathways may prove valuable in many kinds of renal disease.

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Section: Another Final Common Pathway Chronic Hypoxiamentioning

confidence: 87%

Final common pathways of progression of renal diseases

Nangaku

2002

Clinical and Experimental Nephrology

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“…Endostatin is a potent endogenous antiangiogenic factor [29], and a shift in the angiogenic balance toward an increased level endostatin has been observed in experimental models of renal impairment [30,31], and has been shown to exert protective effects to the kidneys of rats with diabetes [12]. In parallel, a shift in the renal angiogenic balance with an upregulation of trombospondin-1, another strong endogenous antiangionic protein, in aged rats with renal impairment has been reported [32]. Our data are in accordance with these experimental observations and suggest a possibility that circulating endostatin to some extent reflects an angiogenic shift in the kidneys.…”

Section: Discussionmentioning

confidence: 99%

Endostatin Level is Associated with Kidney Injury in the Elderly: Findings from Two Community-Based Cohorts

et al. 2014

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Background: We aimed to investigate the associations between circulating endostatin and the different aspects of renal dysfunction, namely, estimated (cystatin C) glomerular filtration rate (GFR) and urine albumin-creatinine ratio (ACR). Methods: Two independent longitudinal community-based cohorts of elderly. ULSAM, n = 786 men; age 78 years; median GFR 74 ml/min/1.73 m²; median ACR 0.80 mg/mmol); and PIVUS, n = 815; age 75 years; 51% women; median GFR; 67 ml/min/1.73 m²; median ACR 1.39 mg/mmol. Cross-sectional associations between the endostatin levels and GFR as well as ACR, and longitudinal association between endostatin at baseline and incident CKD (defined as GFR <60 ml/min/1.73 m²) were assessed. Results: In cross-sectional regression analyses adjusting for age, gender, inflammation, and cardiovascular risk factors, serum endostatin was negatively associated with GFR (ULSAM: B-coefficient per SD increase -0.51, 95% CI (-0.57, -0.45), p < 0.001; PIVUS -0.47, 95% CI (-0.54, -0.41), p < 0.001) and positively associated with ACR (ULSAM: B-coefficient per SD increase 0.24, 95% CI (0.15, 0.32), p < 0.001; PIVUS 0.13, 95% CI (0.06-0.20), p < 0.001) in both cohorts. Moreover, in longitudinal multivariable analyses, higher endostatin levels were associated with increased risk for incident CKD defined as GFR <60 ml/min/1.73 m² at re-investigations in both ULSAM (odds ratio per SD increase of endostatin 1.39 (95% CI 1.01-1.90) and PIVUS 1.68 (95% CI 1.36-2.07)). Conclusions: Higher circulatingendostatin is associated with lower GFR and higher albuminuria and independently predicts incident CKD in elderly subjects. Further studies are warranted to investigate the underlying mechanisms linking endostatin to kidney pathology, and to evaluate the clinical relevance of our findings. i 2014 S. Karger AG, Basel

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“…Insufficient angiogenesis or loss of peritubular and glomerular capillaries has been observed in renal disease models (Kang et al 2001, Basile 2004, indicating that small vessels may play a role in modulating renal injury. It has also been suggested that microvascular plasticity is an active process in renal disease (Lerman & Chade 2009).…”

Section: Discussionmentioning

confidence: 99%

Influence of thyroid state on cardiac and renal capillary density and glomerular morphology in rats

Rodríguez-Gómez

Banegas

Wangensteen

et al. 2012

Journal of Endocrinology

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The purpose was to analyse the cardiac and renal capillary density and glomerular morphology resulting from a chronic excess or deficiency of thyroid hormones (THs) in rats. We performed histopathological, morphometrical and immunohistochemical analyses in hypothyroid and hyperthyroid rats to evaluate the density of mesenteric, renal and cardiac vessels at 4 weeks after induction of thyroid disorders. The main angiogenic factors in plasma, heart and kidney were measured as possible mediators of vascular changes. Mesenteric vessel branching was augmented and decreased in hyper-and hypothyroid rats respectively. The numerical density of CD31-positive capillaries was higher in left and right ventricles and in cortical and medullary kidney from both hyper-and hypothyroid rats vs controls. Numbers of podocytes and glomeruli per square millimetre were similar among groups. Glomerular area and percentage mesangium were greater in the hyperthyroid vs control or hypothyroid groups. No morphological renal lesions were observed in any group. Vascularisation of the mesenteric bed is related to TH levels, but an increased capillarity was observed in heart and kidney in both thyroid disorders. This increase may be produced by higher tissue levels of angiogenic factors in hypothyroid rats, whereas haemodynamic factors would predominate in hyperthyroid rats. Our results also indicate that the renal dysfunctions of thyroid disorders are not related to cortical or medullary microvascular rarefaction and that the proteinuria of hyperthyroidism is not secondary to a podocyte deficit. Finally, TH or its analogues may be useful to increase capillarity in renal diseases associated with microvascular rarefaction.

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Impaired angiogenesis in the aging kidney: Vascular endothelial growth factor and Thrombospondin-1 in renal disease

Cited by 306 publications

References 37 publications

Final common pathways of progression of renal diseases

Final common pathways of progression of renal diseases

Endostatin Level is Associated with Kidney Injury in the Elderly: Findings from Two Community-Based Cohorts

Influence of thyroid state on cardiac and renal capillary density and glomerular morphology in rats

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