title: Matrix metalloproteinase-28 deletion amplifies inflammatory and extracellular matrix responses to cardiac aging.
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.
authors.affiliation: Barshop Institute of Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Ma
authors.forename: Ying Ann
authors.initials: YA
authors.lastname: Chiao
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.forename: Anne M
authors.initials: AM
authors.lastname: Manicone
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Jin
authors.forename: Merry L
authors.initials: ML
authors.lastname: Lindsey
mesh_terms: D000375:Aging; D000818:Animals; D015150:Echocardiography, Doppler; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D006321:Heart / Q000502:physiology* / Q000503:physiopathology; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000378:metabolism; D053505:Matrix Metalloproteinases, Secreted / Q000172:deficiency* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009205:Myocarditis / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology*; D010949:Plasma / Q000737:chemistry
chemical_list: D053505:Matrix Metalloproteinases, Secreted; C477998:Mmp28 protein, mouse