Matrix metalloproteinases (MMP-2,9) and their tissue inhibitors (TIMP-1,2) as novel markers of stress response and atherogenesis in children with chronic kidney disease (CKD) on conservative treatment.
The system of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) may play a key role in atherogenesis of chronic kidney disease (CKD) patients by its impact on matrix accumulation. Connections with inflammation, stress, or endothelial dysfunction are also probable. However, the data on correlations between these parameters in CKD patients are scarce in adults and absent in children. The aim of our study was to evaluate serum concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2, as well as their correlations with markers of stress response (Hsp90-α, anti-Hsp60), endothelial dysfunction (sE-selectin), and inflammation (high-sensitivity C-reactive protein) in CKD children treated conservatively. Thirty-seven patients were divided into two groups according to the CKD stage (gr.CKDI, 19 children with CKD stages 2-3; gr.CKDII, 18 subjects with CKD stages 4-5). Twenty-four age-matched healthy subjects served as controls. Serum concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2, Hsp90-α, anti-Hsp60, and sE-selectin were assessed by ELISA. Median values of MMP-2, MMP-9, TIMP-1, and TIMP-2 were significantly higher in all CKD children vs. controls and were increased in patients with CKD stages 4-5 vs. CKD stages 2-3. Hsp90-α, anti-Hsp60, sE-selectin, and glomerular filtration rate predicted the values of MMPs and TIMPs. Chronic kidney disease in children is characterized by MMP/TIMP system dysfunction, aggravated by the progression of renal failure. Correlations between examined parameters, heat shock proteins, and markers of endothelial damage suggest the possibility of MMP/TIMP application as indicators of stress response and atherogenesis in children with CKD on conservative treatment.
Musiał
Kinga
K
Department of Pediatric Nephrology, Wrocław Medical University, M. Skłodowskiej-Curie 50/52, 50-369, Wrocław, Poland.
Zwolińska
Danuta
D
D000293:Adolescent; D050197:Atherosclerosis / Q000209:etiology*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D019040:E-Selectin / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D018841:HSP90 Heat-Shock Proteins / Q000097:blood; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications* / Q000628:therapy; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood*
D015415:Biomarkers; D019040:E-Selectin; D018841:HSP90 Heat-Shock Proteins; C533585:HSP90AA2P protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D002097:C-Reactive Protein; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
Perit Dial Int. 2010 Mar-Apr;30(2):227-32
20081046
Circulation. 2006 May 23;113(20):2435-44
16702468
J Immunol. 1998 Sep 15;161(6):3071-6
9743373
J Am Soc Nephrol. 2003 Nov;14(11):2861-72
14569096
Nephrol Dial Transplant. 2007 Dec;22(12):3521-6
17636056
Annu Rev Immunol. 2004;22:361-403
15032582
Clin Sci (Lond). 2009 Nov 09;118(4):249-57
19583569
Kidney Blood Press Res. 2009;32(4):276-83
19797911
Atherosclerosis. 2007 Jan;190(1):199-204
16510149
Atherosclerosis. 2008 Jun;198(2):320-31
18054360
Cell Stress Chaperones. 2010 Sep;15(5):675-86
20300983
Arterioscler Thromb Vasc Biol. 2008 Dec;28(12):2108-14
18772495
Am J Physiol Renal Physiol. 2007 Mar;292(3):F905-11
17190907
Cell Stress Chaperones. 2006 Spring;11(1):1-12
16572724
J Clin Invest. 1995 Dec;96(6):2569-77
8675620
Pediatrics. 2004 Aug;114(2 Suppl 4th Report):555-76
15286277
Atherosclerosis. 2008 Nov;201(1):17-32
18585722
Arterioscler Thromb Vasc Biol. 2003 Jun 1;23(6):1060-5
12702515
J Nephrol. 2007 Jul-Aug;20(4):444-52
17879211
Adv Chronic Kidney Dis. 2005 Oct;12(4):397-405
16198279
Fundam Clin Pharmacol. 2005 Dec;19(6):661-7
16313278
Eur J Cardiovasc Prev Rehabil. 2009 Jun;16(3):297-303
19387352
J Intern Med. 2008 May;263(5):464-78
18410590
Circulation. 2009 Sep 1;120(9):792-801
19687355
Arterioscler Thromb Vasc Biol. 2006 May;26(5):1120-5
16556856
Exp Cell Res. 2005 Oct 15;310(1):105-16
16112109
J Clin Invest. 1999 Feb;103(4):571-7
10021466
Cell Stress Chaperones. 2010 Nov;15(6):929-37
20490736
Clin Chim Acta. 2006 Apr;366(1-2):243-8
16313894
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15575-80
16221765
Free Radic Biol Med. 2009 May 1;46(9):1298-307
19248829
FASEB J. 2006 Sep;20(11):1898-900
16891619
Circ Res. 2010 Mar 5;106(4):796-808
20056917
Atherosclerosis. 2010 Feb;208(2):557-63
19748093
Circulation. 2004 Mar 23;109(11):1408-14
14993123
Arterioscler Thromb Vasc Biol. 2006 Feb;26(2):340-6
16306430
Cardiovasc Res. 2010 May 1;86(2):330-7
20154064
Cell Stress Chaperones. 1999 Mar;4(1):29-35
10467106
Atherosclerosis. 2009 Nov;207(1):74-83
19481753
Nephron. 2002 Dec;92(4):817-23
12399626
Exp Nephrol. 2002;10(3):182-95
12053120
Ann N Y Acad Sci. 2007 Jun;1107:1-10
17804527
Clin Chim Acta. 2006 Apr;366(1-2):185-9
16280123