Faculty Collaboration Database

Angiostatin and matrix metalloprotease expression following ischemic acute renal failure. Am J Physiol Renal Physiol 2004 May;286(5):F893-902

Date

04/13/2004

Pubmed ID

15075185

DOI

10.1152/ajprenal.00328.2003

Scopus ID

2-s2.0-1942535190 (requires institutional sign-in at Scopus site)   116 Citations

Abstract

Ischemic injury to the kidney results in blood vessel loss and predisposition to chronic renal disease. Angiostatin is a proteolytic cleavage product of plasminogen that inhibits angiogenesis, promotes apoptosis of endothelial cells, and disrupts capillary integrity. A combination of lysine-Sepharose enrichment followed by Western blotting was used to study the expression of angiostatin in response to the induction of ischemic renal injury. No angiostatin products were readily detectable in kidneys of sham-operated control rats. In contrast, both 38- and 50-kDa forms of angiostatin were dramatically enhanced in the first 3 days following 45-min ischemia-reperfusion injury. Renal angiostatin levels declined but remained detectable at late time points postrecovery (8-35 days postischemia). Angiostatin-like immunoreactivity was also elevated in the plasma and in urine for up to 35 days following injury. Lysine-Sepharose extracts of either kidney or urine inhibited vascular endothelial cell growth factor-induced proliferation of human aortic endothelial cells in vitro; an effect that was blocked by coincubation with an angiostatin antibody. RT-PCR verified that mRNA of the parent protein plasminogen was produced in the liver, but it was not present in either sham-operated or postischemic kidney. Matrix metalloproteinase (MMP)-2 and MMP-9, which may mediate angiostatin generation, were enhanced in postischemic kidney tissue and were localized to the renal tubules, interstitial cells, and the tubulo-interstitial space. These data indicate the possible local synthesis of angiostatin following acute renal failure (ARF) and suggest a possible role for MMPs in this activity. Renal angiostatin generation following ARF may modulate renal capillary density postischemia and thereby influence chronic renal function.

Author List

Basile DP, Fredrich K, Weihrauch D, Hattan N, Chilian WM

Author

Dorothee Weihrauch DVM, PhD Research Scientist II in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Kidney Injury
Affinity Labels
Angiostatins
Animals
Antibodies
Extracellular Matrix
Gene Expression
Ischemia
Kidney
Male
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Plasminogen
RNA, Messenger
Rats
Rats, Sprague-Dawley
Sepharose