TY - JOUR
T1 - Age-dependent changes in myocardial matrix metalloproteinase/tissue inhibitor of metalloproteinase profiles and fibroblast function
AU - Lindsey, Merry L.
AU - Goshorn, Danielle K.
AU - Squires, Christina E.
AU - Escobar, G. Patricia
AU - Hendrick, Jennifer W.
AU - Mingoia, Joseph T.
AU - Sweterlitsch, Sarah E.
AU - Spinale, Francis G.
N1 - Funding Information:
The authors acknowledge the following sources of support: HL-10337 (MLL), HL-75360 (MLL), HL-45024 (FGS), HL-97012 (FGS), P01-48788 (FGS), and a VA Career Development Award (FGS).
PY - 2005/5/1
Y1 - 2005/5/1
N2 - 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.
AB - 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.
KW - Extracellular matrix
KW - Matrix metalloproteinase
KW - Matrix remodeling
KW - Tissue inhibitor of metalloproteinase
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U2 - 10.1016/j.cardiores.2004.11.029
DO - 10.1016/j.cardiores.2004.11.029
M3 - Review article
C2 - 15820210
AN - SCOPUS:16344385466
SN - 0008-6363
VL - 66
SP - 410
EP - 419
JO - Cardiovascular research
JF - Cardiovascular research
IS - 2
ER -