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

Merry L. Lindsey, Danielle K. Goshorn, Christina E. Squires, G. Patricia Escobar, Jennifer W. Hendrick, Joseph T. Mingoia, Sarah E. Sweterlitsch, Francis G. Spinale

Research output: Contribution to journalReview article

115 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)410-419
Number of pages10
JournalCardiovascular research
Volume66
Issue number2
DOIs
StatePublished - May 1 2005

Fingerprint

Tissue Inhibitor of Metalloproteinases
Matrix Metalloproteinase Inhibitors
Collagen
Fibroblasts
Extracellular Matrix
Matrix Metalloproteinase 12
Tissue Inhibitor of Metalloproteinase-3
Matrix Metalloproteinase 8
Matrix Metalloproteinase 14
Matrix Metalloproteinase 3
Matrix Metalloproteinase 9
Immunoblotting
Proteins

Keywords

  • Extracellular matrix
  • Matrix metalloproteinase
  • Matrix remodeling
  • Tissue inhibitor of metalloproteinase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Age-dependent changes in myocardial matrix metalloproteinase/tissue inhibitor of metalloproteinase profiles and fibroblast function. / Lindsey, Merry L.; Goshorn, Danielle K.; Squires, Christina E.; Escobar, G. Patricia; Hendrick, Jennifer W.; Mingoia, Joseph T.; Sweterlitsch, Sarah E.; Spinale, Francis G.

In: Cardiovascular research, Vol. 66, No. 2, 01.05.2005, p. 410-419.

Research output: Contribution to journalReview article

Lindsey, Merry L. ; Goshorn, Danielle K. ; Squires, Christina E. ; Escobar, G. Patricia ; Hendrick, Jennifer W. ; Mingoia, Joseph T. ; Sweterlitsch, Sarah E. ; Spinale, Francis G. / Age-dependent changes in myocardial matrix metalloproteinase/tissue inhibitor of metalloproteinase profiles and fibroblast function. In: Cardiovascular research. 2005 ; Vol. 66, No. 2. pp. 410-419.
@article{263ce7957c03403a8c8b8ee04fe2711f,
title = "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.",
keywords = "Extracellular matrix, Matrix metalloproteinase, Matrix remodeling, Tissue inhibitor of metalloproteinase",
author = "Lindsey, {Merry L.} and Goshorn, {Danielle K.} and Squires, {Christina E.} and Escobar, {G. Patricia} and Hendrick, {Jennifer W.} and Mingoia, {Joseph T.} and Sweterlitsch, {Sarah E.} and Spinale, {Francis G.}",
year = "2005",
month = "5",
day = "1",
doi = "10.1016/j.cardiores.2004.11.029",
language = "English (US)",
volume = "66",
pages = "410--419",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "2",

}

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.

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

UR - http://www.scopus.com/inward/record.url?scp=16344385466&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=16344385466&partnerID=8YFLogxK

U2 - 10.1016/j.cardiores.2004.11.029

DO - 10.1016/j.cardiores.2004.11.029

M3 - Review article

C2 - 15820210

AN - SCOPUS:16344385466

VL - 66

SP - 410

EP - 419

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 2

ER -