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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 ,
Ying Ann Chiao ,
Jianhua Zhang ,
Anne M. Manicone ,
Yu-Fang Jin  and
Merry L. Lindsey
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: lindseym@uthscsa.edu
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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.

Keywords

MMP-28cardiac agingextracellular matrixinflammationmacrophagecollagenleft ventriclemice
Type
Feature Article
Information
Microscopy and Microanalysis , Volume 18 , Issue 1 , February 2012 , pp. 81 - 90
Copyright
Copyright © Microscopy Society of America 2012

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