期刊
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
卷 296, 期 1, 页码 F145-F152出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.90430.2008
关键词
angiogenesis; gene therapy; inflammation; macrophage; vascular growth factors
资金
- National Institutes of Health [DK-52121, HL-68607]
- Gatorade funds
- Kidney Research UK Senior Non-Clinical Fellowship
- Kidney Research UK [SF1/2008] Funding Source: researchfish
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL068607] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK052121] Funding Source: NIH RePORTER
Mu W, Long DA, Ouyang X, Agarwal A, Cruz PE, Roncal CA, Nakagawa T, Yu X, Hauswirth WW, Johnson RJ. Angiostatin overexpression is associated with an improvement in chronic kidney injury by an anti-inflammatory mechanism. Am J Physiol Renal Physiol 296: F145-F152, 2009. First published October 29, 2008; doi: 10.1152/ajprenal.90430.2008.-Angiostatin, a proteolytic fragment of plasminogen, is a potent anti-angiogenic factor recently shown also to have an inhibitory effect on leukocyte recruitment and macrophage migration. Because both angiogenesis and inflammation play key roles in the progression of chronic kidney disease, we evaluated the effect of angiostatin treatment in the rat remnant kidney model. Rats were pretreated for 4 wk with recombinant adeno-associated viruses expressing either angiostatin or green fluorescence protein. Chronic renal disease was then induced by a subtotal nephrectomy, and rats were killed 8 wk later for analysis. Angiostatin treatment was associated with significantly less proteinuria but no alterations in serum creatinine, creatinine clearance, and blood urea nitrogen levels. Treatment with angiostatin reduced renal peritubular capillary number and decreased urinary nitric oxide levels. Despite reducing capillary density, angiostatin diminished interstitial fibrosis in association with reduced macrophage and T-cell infiltration and renal monocyte chemoattractant protein-1 mRNA levels. In conclusion, angiostatin overexpression was associated with attenuated renal disease progression in a model of chronic kidney injury, likely because of its anti-inflammatory actions. However, its anti-angiogenic actions suggest countering effects that could partially offset its benefit in chronic kidney diseases.
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