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Matrix Metalloproteinase-28 Deletion Amplifies Inflammatory and Extracellular Matrix Responses to Cardiac Aging

Published online by Cambridge University Press:  08 December 2011

Yonggang Ma
Affiliation:
Barshop Institute of Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA Division of Geriatrics, Gerontology and Palliative Medicine, Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA
Ying Ann Chiao
Affiliation:
Barshop Institute of Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA Division of Geriatrics, Gerontology and Palliative Medicine, Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA Department of Biochemistry, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA
Jianhua Zhang
Affiliation:
Barshop Institute of Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA Division of Geriatrics, Gerontology and Palliative Medicine, Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA
Anne M. Manicone
Affiliation:
Center for Lung Biology and Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA 98109, USA
Yu-Fang Jin
Affiliation:
Department of Electrical and Computer Engineering, The University of Texas at San Antonio, San Antonio, TX 78245, USA
Merry L. Lindsey*
Affiliation:
Barshop Institute of Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA Division of Geriatrics, Gerontology and Palliative Medicine, Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA
*
Corresponding author. E-mail: [email protected]
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Abstract

To determine if matrix metalloproteinase (MMP)-28 mediates cardiac aging, wild-type (WT) and MMP-28−/− young (7 ± 1 months, n = 9 each) and old (20 ± 2 months, n = 7 each) female mice were evaluated. MMP-28 expression in the left ventricle (LV) increased 42% in old WT mice compared to young controls (p < 0.05). By Doppler echocardiography, LV function declined at 20 ± 2 months of age for both groups. However, dobutamine stress responses were similar, indicating that cardiac reserve was maintained. Plasma proteomic profiling revealed that macrophage inflammatory protein (MIP)-1 α, MIP-1β and MMP-9 plasma levels did not change in WT old mice but were significantly elevated in MMP-28−/− old mice (all p < 0.05), suggestive of a higher inflammatory status when MMP-28 is deleted. RT2-PCR gene array and immunoblotting analyses demonstrated that MIP-1α and MMP-9 gene and protein levels in the LV were also higher in MMP-28−/− old mice (all p < 0.05). Macrophage numbers in the LV increased similarly in WT and MMP-28−/− old mice, compared to respective young controls (both p < 0.05). Collagen content was not different among the WT and MMP-28−/− young and old mice. In conclusion, LV inflammation increases with age, and MMP-28 deletion further elevates inflammation and extracellular matrix responses, without altering macrophage numbers or collagen content.

Type
Feature Article
Copyright
Copyright © Microscopy Society of America 2012

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References

REFERENCES

Angomachalelis, N., Hourzamanis, A., Vakalis, D., Vamvalis, C., Serasli, E. & Siourthas, D. (1994). Acoustic quantification: New diastolic indices of left ventricular function in hypertension correlation with Doppler echocardiography. Postgrad Med J 70(S1), S57S66.Google ScholarPubMed
Bassi, D.E., Fu, J., Lopez de Cicco, R. & Klein-Szanto, A.J. (2005). Proprotein convertases: “Master switches” in the regulation of tumor growth and progression. Mol Carcinog 44(3), 151161.CrossRefGoogle ScholarPubMed
Bister, V.O., Salmela, M.T., Karjalainen-Lindsberg, M.L., Uria, J., Lohi, J., Puolakkainen, P., Lopez-Otin, C. & Saarialho-Kere, U. (2004). Differential expression of three matrix metalloproteinases, MMP-19, MMP-26, and MMP-28, in normal and inflamed intestine and colon cancer. Dig Dis Sci 49(4), 653661.CrossRefGoogle ScholarPubMed
Chen, W. & Frangogiannis, N.G. (2010). The role of inflammatory and fibrogenic pathways in heart failure associated with aging. Heart Fail Rev 15(5), 415422.CrossRefGoogle ScholarPubMed
Dai, D.F. & Rabinovitch, P.S. (2009). Cardiac aging in mice and humans: The role of mitochondrial oxidative stress. Trends Cardiovasc Med 19(7), 213220.CrossRefGoogle ScholarPubMed
de Jager, S.C., Kraaijeveld, A.O., Grauss, R.W., de Jager, W., Liem, S.S., van der Hoeven, B.L., Prakken, B.J., Putter, H., van Berkel, T.J., Atsma, D.E., Schalij, M.J., Jukema, J.W. & Biessen, E.A. (2008). CCL3 (MIP-1 alpha) levels are elevated during acute coronary syndromes and show strong prognostic power for future ischemic events. J Mol Cell Cardiol 45(3), 446452.CrossRefGoogle ScholarPubMed
Frangogiannis, N.G. (2004). Chemokines in the ischemic myocardium: From inflammation to fibrosis. Inflamm Res 53(11), 585595.CrossRefGoogle ScholarPubMed
Godfrey, P., Rahal, J.O., Beamer, W.G., Copeland, N.G., Jenkins, N.A. & Mayo, K.E. (1993). GHRH receptor of little mice contains a missense mutation in the extracellular domain that disrupts receptor function. Nat Genet 4(3), 227232.CrossRefGoogle ScholarPubMed
Goser, S., Ottl, R., Brodner, A., Dengler, T.J., Torzewski, J., Egashira, K., Rose, N.R., Katus, H.A. & Kaya, Z. (2005). Critical role for monocyte chemoattractant protein-1 and macrophage inflammatory protein-1alpha in induction of experimental autoimmune myocarditis and effective anti-monocyte chemoattractant protein-1 gene therapy. Circulation 112(22), 34003407.CrossRefGoogle ScholarPubMed
Illman, S.A., Keski-Oja, J., Parks, W.C. & Lohi, J. (2003). The mouse matrix metalloproteinase, epilysin (MMP-28), is alternatively spliced and processed by a furin-like proprotein convertase. Biochem J 375(Pt 1), 191197.CrossRefGoogle ScholarPubMed
Illman, S.A., Lehti, K., Keski-Oja, J. & Lohi, J. (2006). Epilysin (MMP-28) induces TGF-beta mediated epithelial to mesenchymal transition in lung carcinoma cells. J Cell Sci 119(Pt 18), 38563865.CrossRefGoogle ScholarPubMed
Illman, S.A., Lohi, J. & Keski-Oja, J. (2008). Epilysin (MMP-28)—Structure, expression and potential functions. Exp Dermatol 17(11), 897907.CrossRefGoogle ScholarPubMed
Iwanaga, Y., Aoyama, T., Kihara, Y., Onozawa, Y., Yoneda, T. & Sasayama, S. (2002). Excessive activation of matrix metalloproteinases coincides with left ventricular remodeling during transition from hypertrophy to heart failure in hypertensive rats. J Am Coll Cardiol 39(8), 13841391.CrossRefGoogle ScholarPubMed
Kasama, T., Yajima, N., Matsukura, S. & Adachi, M. (2006). Macrophage inflammatory protein 1 and CCR5 as attractive therapeutic targets for HIV infection. Recent Pat Antiinfect Drug Discov 1(3), 275280.CrossRefGoogle ScholarPubMed
Kevorkian, L., Young, D.A., Darrah, C., Donell, S.T., Shepstone, L., Porter, S., Brockbank, S.M., Edwards, D.R., Parker, A.E. & Clark, I.M. (2004). Expression profiling of metalloproteinases and their inhibitors in cartilage. Arthritis Rheum 50(1), 131141.CrossRefGoogle ScholarPubMed
Lakatta, E.G. & Levy, D. (2003). Arterial and cardiac aging: Major shareholders in cardiovascular disease enterprises: Part I: Aging arteries: a “set up” for vascular disease. Circulation 107(1), 139146.CrossRefGoogle ScholarPubMed
Lin, J., Lopez, E.F., Jin, Y., Van Remmen, H., Bauch, T., Han, H.C. & Lindsey, M.L. (2008). Age-related cardiac muscle sarcopenia: Combining experimental and mathematical modeling to identify mechanisms. Exp Gerontol 43(4), 296306.CrossRefGoogle ScholarPubMed
Lin, M.H., Liu, S.Y., Su, H.J. & Liu, Y.C. (2006). Functional role of matrix metalloproteinase-28 in the oral squamous cell carcinoma. Oral Oncol 42(9), 907913.CrossRefGoogle ScholarPubMed
Lindsey, M.L. (2004). MMP induction and inhibition in myocardial infarction. Heart Fail Rev 9(1), 719.CrossRefGoogle ScholarPubMed
Lindsey, M.L. (2006). Novel strategies to delineate matrix metalloproteinase (MMP)-substrate relationships and identify targets to block MMP activity. Mini Rev Med Chem 6(11), 12431248.CrossRefGoogle ScholarPubMed
Lindsey, M.L., Escobar, G.P., Dobrucki, L.W., Goshorn, D.K., Bouges, S., Mingoia, J.T., McClister, D.M. Jr., Su, H., Gannon, J., MacGillivray, C., Lee, R.T., Sinusas, A.J. & Spinale, F.G. (2006). Matrix metalloproteinase-9 gene deletion facilitates angiogenesis after myocardial infarction. Am J Physiol Heart Circ Physiol 290(1), H232H239.CrossRefGoogle ScholarPubMed
Lindsey, M.L., Mann, D.L., Entman, M.L. & Spinale, F.G. (2003). Extracellular matrix remodeling following myocardial injury. Ann Med 35(5), 316326.CrossRefGoogle ScholarPubMed
Lohi, J., Wilson, C.L., Roby, J.D. & Parks, W.C. (2001). Epilysin, a novel human matrix metalloproteinase (MMP-28) expressed in testis and keratinocytes and in response to injury. J Biol Chem 276(13), 1013410144.CrossRefGoogle ScholarPubMed
Manicone, A.M., Birkland, T.P., Lin, M., Betsuyaku, T., van Rooijen, N., Lohi, J., Keski-Oja, J., Wang, Y., Skerrett, S.J. & Parks, W.C. (2009). Epilysin (MMP-28) restrains early macrophage recruitment in Pseudomonas aeruginosa pneumonia. J Immunol 182(6), 38663876.CrossRefGoogle ScholarPubMed
Marchenko, G.N. & Strongin, A.Y. (2001). MMP-28, a new human matrix metalloproteinase with an unusual cysteine-switch sequence is widely expressed in tumors. Gene 265(1-2), 8793.CrossRefGoogle ScholarPubMed
Nishimura, M., Ocorr, K., Bodmer, R. & Cartry, J. (2011). Drosophila as a model to study cardiac aging. Exp Gerontol 46(5), 326330.CrossRefGoogle Scholar
Onal, I.K., Altun, B., Onal, E.D., Kirkpantur, A., Gul Oz, S. & Turgan, C. (2009). Serum levels of MMP-9 and TIMP-1 in primary hypertension and effect of antihypertensive treatment. Eur J Intern Med 20(4), 369372.CrossRefGoogle ScholarPubMed
Overall, C.M., Tam, E.M., Kappelhoff, R., Connor, A., Ewart, T., Morrison, C.J., Puente, X., Lopez-Otin, C. & Seth, A. (2004). Protease degradomics: Mass spectrometry discovery of protease substrates and the CLIP-CHIP, a dedicated DNA microarray of all human proteases and inhibitors. Biol Chem 385(6), 493504.CrossRefGoogle ScholarPubMed
Pavlaki, M., Zucker, S., Dufour, A., Calabrese, N., Bahou, W. & Cao, J. (2011). Furin functions as a nonproteolytic chaperone for matrix metalloproteinase-28: MMP-28 propeptide sequence requirement. Biochem Res Int 2011, 630319.CrossRefGoogle ScholarPubMed
Polyakova, V., Loeffler, I., Hein, S., Miyagawa, S., Piotrowska, I., Dammer, S., Risteli, J., Schaper, J. & Kostin, S. (2011). Fibrosis in endstage human heart failure: Severe changes in collagen metabolism and MMP/TIMP profiles. Int J Cardiol 151(1), 1833.CrossRefGoogle ScholarPubMed
Reddy, A.K., Amador-Noguez, D., Darlington, G.J., Scholz, B.A., Michael, L.H., Hartley, C.J., Entman, M.L. & Taffet, G.E. (2007). Cardiac function in young and old Little mice. J Gerontol A Biol Sci Med Sci 62(12), 13191325.CrossRefGoogle Scholar
Reddy, A.K., Taffet, G.E., Li, Y.H., Lim, S.W., Pham, T.T., Pocius, J.S., Entman, M.L., Michael, L.H. & Hartley, C.J. (2005). Pulsed Doppler signal processing for use in mice: Applications. IEEE Trans Biomed Eng 52(10), 17711783.CrossRefGoogle ScholarPubMed
Reno, F., Sabbatini, M., Stella, M., Magliacani, G. & Cannas, M. (2005). Effect of in vitro mechanical compression on Epilysin (matrix metalloproteinase-28) expression in hypertrophic scars. Wound Repair Regen 13(3), 255261.CrossRefGoogle ScholarPubMed
Reynolds, J.L., Mahajan, S.D., Aalinkeel, R., Nair, B., Sykes, D.E. & Schwartz, S.A. (2011). Methamphetamine and HIV-1 gp120 effects on lipopolysaccharide stimulated matrix metalloproteinase-9 production by human monocyte-derived macrophages. Immunol Invest 40(5), 481497.CrossRefGoogle ScholarPubMed
Saarialho-Kere, U., Kerkela, E., Jahkola, T., Suomela, S., Keski-Oja, J. & Lohi, J. (2002). Epilysin (MMP-28) expression is associated with cell proliferation during epithelial repair. J Invest Dermatol 119(1), 1421.CrossRefGoogle ScholarPubMed
Spinale, F.G., Coker, M.L., Bond, B.R. & Zellner, J.L. (2000). Myocardial matrix degradation and metalloproteinase activation in the failing heart: a potential therapeutic target. Cardiovasc Res 46(2), 225238.CrossRefGoogle ScholarPubMed
Thomas, D.P., Zimmerman, S.D., Hansen, T.R., Martin, D.T. & McCormick, R.J. (2000). Collagen gene expression in rat left ventricle: Interactive effect of age and exercise training. J Appl Physiol 89(4), 14621468.CrossRefGoogle ScholarPubMed
Zamilpa, R., Kanakia, R., Cigarroa, J.T., Dai, Q., Escobar, G.P., Martinez, H., Jimenez, F., Ahuja, S.S. & Lindsey, M.L. (2011). CC chemokine receptor 5 deletion impairs macrophage activation and induces adverse remodeling following myocardial infarction. Am J Physiol Heart Circ Physiol 300(4), H1418H1426.CrossRefGoogle ScholarPubMed