Expression of urokiase-type plasminogen activator and matrix metalloproteinases in human tissue of abdominal aortic aneurysm

Abstract

Abstract: Objective To explore the expression of urokinase-type plasminogen activator (u-PA) and matrix metalloproteinases in human abdominal aortic aneurysm (AAA) tissue. Methods Immunohistochemistry and in situ hybridization were employed to detect the protein and mRNA expression of u-PA, gelatinase A (MMP-2) and gelatinase B (MMP-9) in the tissue sections of 30 AAA specimens and 30 normal human abdominal aorta specimens. Results The expressions of u-PA and MMP-9 were mainly found in the macrophages in AAA tissue, but not in normal human abdominal aorta tissues. The expression of MMP-2 was found mainly in the smooth muscle cells in AAA tissues, but not in normal human abdominal aorta tissues. Conclusion u-PA produced by macrophages may immediately activate proMMP-2 and proMMP-9, which play a pivotal role in the formation and development of AAA.

CLC Number:

LI Yan¹, ZHANG Ye-wei². Expression of urokiase-type plasminogen activator and matrix metalloproteinases in human tissue of abdominal aortic aneurysm[J]. Journal of Southern Medical University, 2005, 25(10): 1305-1307,1311.

References

[1] Maggiano N, Larocca LM, Pinntelli M, et al. Detection of mRNA and hnRNA using a digoxigenin labeled cDNA probe by in situ hybridization on frozen tissue sections [J]. Histochem J, 1991, 23(19): 69-74.
[2] Carmeliet P, Moons L, Lijnen R, et al. Urokinase-generated plasmin activates matrixmetalloproteinases during aneurysm formation [J].Nat Genet, 1997, 17(11): 439-44.
[3] Shah PK. Inflammation, metalloproteinases, and increased proteolysis: an emerging pathophysiological paradigm in aortic aneurysm [J]. Circulation, 1997, 96(9): 2115-7.
[4] Thompson RW, Parks WC. Role of matrix meralloproteinases in abdominal aortic aneurysms [J]. Ann N Y Acad Sci, 1996, 800(11):157-74.
[5] Migntti P. Extracellular matrix remodeling by metallopro teinases abd okasminogen activators [J]. Kidney Int, 1995, 47(Suppl 49):12-4.
[6] Roldan AL, Cubellis MV, Masucci MT, et al. Cloning and expression of the receptor for humanurokonase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis [J].EMBO J, 1999, 16(21): 467-74.
[7] Vassali JD, Baccino D, Belin D, et al. A cellular binding site for the Mr 55,000 form of the human plasminogen activator, urokinaes [J].J Cell Biol, 1985, 100(12): 86-92.
[8] Ellis V, Behrendt N, Dano K, et al. Plasminogen activation by receptor-bound urokinase, a kinetic study with both cell-associated and isolated receptor[J]. J Biol Chem, 1991, 266: 12752-8.
[9] Anidjar S, Salzmann JL, Gentric D, et al. Elastase induces experimentalaneurysms in rats [J]. Circulation, 2001, 82 (14):973-81.
[10] Matrisian LM. The matrix-degrading metalloproteinases [J]. Bioessays, 1992, 14(7): 455-62.
[11] Birkedal-Hansen H. Proteolytic remodeling ofextracellular matrix [J]. Cuur Opin Cell Biol, 1995, 7(7): 728-35.
[12] Okada Y, Agonoji Y, Naka K, et al. Matrix metalloproteinaes 9 (92 kDa gelatinase/type Ⅳ collagenase) from HT1080 human fibrosarcoma cells, purification and activation of the precursor and enxymic properties[J]. J Biol Chem, 1992, 267(14): 21712-9.
[13] Suxuki K, Eenhild J J, Morodomi T, et al. Mechanisms of activation of tissue procollagenase by metalloproteinase 3 (stomelysin) [J].Biochemistry, 1990, 29(9): 10261-70.
[14] Mazzieri R, Masiero L, Zanetta L, et al. Control of type Ⅳ collagenase activity by components of the urokinase-plasmin system regulatory mechanism with cell-bound reactants[J]. EMBO J, 2003,16(9): 2319-32.
[15] Mignatti P, Tsuboi R, Robbins E, et al. In vitro angiogenesis on the human amniotic membrane: requirement for basic fibroblast growth factor induced proteinases [J]. J Cell Biol, 2004, 108( 13): 671-82.
[16] Galis ZS, Muszynski M, Sukhova GK, et al. Cytokine-stimulated human vascular smooth muscle cells synthesize accomplishment of enzymes required for extracellular matrix digestion [J]. Circ Res,1994, 75(1): 181-89.
[17] Herron S, Unemori E, Wong M, et al. Connective tissue proteinases and inhibitor in abdominal aortic aneurysms, involvement of the vase vasorum in the pathogenesis of aortic anuysms [J]. Arterioscler Thromb Vasc Biol, 2001, 11(1): 1667-77.
[18] Szekanecz Z, Shah MR, Harlow LA, et al. Interleukin-8 and tumor necrosis factor-are involved in human aortic endothelial cell migration[J]. Pathobiology, 2004, 62(3): 134-9.
[19] White JV, Haas K, Phillips S, et al. Adventitial elastolysis is a primary event in aneurysm formation [J]. J Vasc Surg, 2003, 17(2):371-80.