TY - JOUR
T1 - The impact of age on cardiac function and extracellular matrix component expression in adverse post-infarction remodeling in mice
AU - Nagel, Felix
AU - Santer, David
AU - Stojkovic, Stefan
AU - Kaun, Christoph
AU - Schaefer, Anne-Kristin
AU - Krššák, Martin
AU - Abraham, Dietmar
AU - Bencsik, Péter
AU - Ferdinandy, Péter
AU - Kenyeres, Eva
AU - Szabados, Tamara
AU - Wojta, Johann
AU - Trescher, Karola
AU - Kiss, Attila
AU - Podesser, Bruno K
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/5
Y1 - 2019/5
N2 - The aim of this study was to describe the potential associations of the expression of matricellular components in adverse post-infarction remodeling of the geriatric heart. In male geriatric (OM, age: 18 months) and young (YM, age: 11 weeks) OF1 mice myocardial infarction (MI) was induced by permanent ligation of the left anterior descending coronary artery. Cardiac function was evaluated by MRI. Plasma and myocardial tissue samples were collected 3d, 7d, and 32d post-MI. Age and MI were associated with impaired cardiac function accompanied by left-ventricular (LV) dilatation. mRNA expression of MMP-2 (7d: p < 0.05), TIMP-1 (7d: p < 0.05), TIMP-2 (7d: p < 0.05), Collagen-1 (3d and 7d: p < 0.05) and Collagen-3 (7d: p < 0.05) in LV non-infarcted myocardium was significantly higher in YM than in OM after MI. MMP-9 activity in plasma was increased in OM after MI (3d: p < 0.01). Tenascin-C protein levels assessed by ELISA were decreased in OM as compared to YM after MI in plasma (3d: p < 0.001, 7d: p < 0.05) and LV non-infarcted myocardium (7d: p < 0.01). Dysregulation in ECM components in non-infarcted LV might be associated and contribute to adverse LV remodeling and impaired cardiac function. Thus, targeting ECM might be a potential therapeutic approach to enhance cardiac function in geriatric patients following MI.
AB - The aim of this study was to describe the potential associations of the expression of matricellular components in adverse post-infarction remodeling of the geriatric heart. In male geriatric (OM, age: 18 months) and young (YM, age: 11 weeks) OF1 mice myocardial infarction (MI) was induced by permanent ligation of the left anterior descending coronary artery. Cardiac function was evaluated by MRI. Plasma and myocardial tissue samples were collected 3d, 7d, and 32d post-MI. Age and MI were associated with impaired cardiac function accompanied by left-ventricular (LV) dilatation. mRNA expression of MMP-2 (7d: p < 0.05), TIMP-1 (7d: p < 0.05), TIMP-2 (7d: p < 0.05), Collagen-1 (3d and 7d: p < 0.05) and Collagen-3 (7d: p < 0.05) in LV non-infarcted myocardium was significantly higher in YM than in OM after MI. MMP-9 activity in plasma was increased in OM after MI (3d: p < 0.01). Tenascin-C protein levels assessed by ELISA were decreased in OM as compared to YM after MI in plasma (3d: p < 0.001, 7d: p < 0.05) and LV non-infarcted myocardium (7d: p < 0.01). Dysregulation in ECM components in non-infarcted LV might be associated and contribute to adverse LV remodeling and impaired cardiac function. Thus, targeting ECM might be a potential therapeutic approach to enhance cardiac function in geriatric patients following MI.
KW - Aging/genetics
KW - Animals
KW - Disease Models, Animal
KW - Extracellular Matrix/metabolism
KW - Magnetic Resonance Imaging
KW - Male
KW - Matrix Metalloproteinase 2/genetics
KW - Matrix Metalloproteinase 9/blood
KW - Mice
KW - Myocardial Infarction/genetics
KW - RNA, Messenger/genetics
KW - Tenascin/blood
KW - Tissue Inhibitor of Metalloproteinase-1/genetics
KW - Tissue Inhibitor of Metalloproteinase-2/genetics
KW - Ventricular Remodeling/genetics
UR - http://www.scopus.com/inward/record.url?scp=85061812734&partnerID=8YFLogxK
U2 - 10.1016/j.exger.2019.02.008
DO - 10.1016/j.exger.2019.02.008
M3 - Journal article
C2 - 30763602
SN - 0531-5565
VL - 119
SP - 193
EP - 202
JO - Experimental Gerontology
JF - Experimental Gerontology
ER -