Age-dependent changes in myocardial matrix metalloproteinase/tissue inhibitor of metalloproteinase profiles and fibroblast function.

Abstract:

OBJECTIVE:To evaluate the effects of aging on left ventricular (LV) geometry, collagen levels, matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) abundance, and myocardial fibroblast function. METHODS:Young (3-month-old; n=28), middle-aged (MA; 15-month-old; n=17), and old (23-month-old; n=16) CB6F1 mice of both sexes were used in this study. Echocardiographic parameters were measured; collagen, MMP, and TIMP levels were determined for both the soluble and insoluble protein fractions; and fibroblast function was evaluated. RESULTS:LV end-diastolic dimensions and wall thickness increased in both MA and old mice, accompanied by increased soluble protein and decreased insoluble collagen. Immunoblotting revealed differential MMP/TIMP profiles. Compared to MA levels, MMP-3, MMP-8, MMP-9, MMP-12, and MMP-14 increased, and TIMP-3 and TIMP-4 decreased in the insoluble fraction of old mice, suggesting increased extracellular matrix (ECM) degradative capacity. Fibroblast proliferation was blunted with age. CONCLUSION:This study, for the first time, identified specific differences in cellular and extracellular processes that likely contribute to age-dependent ECM remodeling.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Lindsey ML,Goshorn DK,Squires CE,Escobar GP,Hendrick JW,Mingoia JT,Sweterlitsch SE,Spinale FG

doi

10.1016/j.cardiores.2004.11.029

subject

Has Abstract

pub_date

2005-05-01 00:00:00

pages

410-9

issue

2

eissn

0008-6363

issn

1755-3245

pii

S0008-6363(04)00524-3

journal_volume

66

pub_type

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