TY - JOUR
T1 - Lack of effect of prolonged treatment with liraglutide on cardiac remodeling in rats after acute myocardial infarction
AU - Kyhl, Kasper
AU - Lønborg, Jacob
AU - Hartmann, Bolette
AU - Kissow, Hannelouise
AU - Poulsen, Steen Seier
AU - Ali, Henrik El
AU - Kjær, Andreas
AU - Dela, Flemming
AU - Engstrøm, Thomas
AU - Treiman, Marek
PY - 2017
Y1 - 2017
N2 - Following the acute phase of a myocardial infarction, a set of structural and functional changes evolves in the myocardium, collectively referred to as cardiac remodeling. This complex set of processes, including interstitial fibrosis, inflammation, myocyte hypertrophy and apoptosis may progress to heart failure. Analogs of the incretin hormone glucagon-like peptide 1 (GLP-1) have shown some promise as cardioprotective agents. We hypothesized that a long-acting GLP-1 analog liraglutide would ameliorate cardiac remodeling over the course of 4 weeks in a rat model of non-reperfused myocardial infarction. In 134 male Sprague Dawley rats myocardial infarctions were induced by ligation of the left anterior descending coronary artery. Rats were randomized to either subcutaneous injection of placebo or 0.3. mg liraglutide once daily. Cardiac magnetic resonance imaging was performed after 4 weeks. Histology of the infarcted and remote non-infarcted myocardium, selected molecular remodeling markers and mitochondrial respiration in fibers of remote non-infarcted myocardium were analyzed. Left ventricular end diastolic volume increased in the infarcted hearts by 62% (from 0.58. ±. 0.03. mL to 0.95. ±. 0.07. mL, P. <. 0.05) compared to sham operated hearts and left ventricle ejection fraction decreased by 37% (63. ±. 1%-40. ±. 3%, P. <. 0.05). Increased interstitial fibrosis and phosphorylation of p38 Mitogen Activated Protein Kinase were observed in the non-infarct regions. Mitochondrial fatty acid oxidation was impaired. Liraglutide did not affect any of these alterations. Four-week treatment with liraglutide did not affect cardiac remodeling following a non-reperfused myocardial infarction, as assessed by cardiac magnetic resonance imaging, histological and molecular analysis and measurements of mitochondrial respiration.
AB - Following the acute phase of a myocardial infarction, a set of structural and functional changes evolves in the myocardium, collectively referred to as cardiac remodeling. This complex set of processes, including interstitial fibrosis, inflammation, myocyte hypertrophy and apoptosis may progress to heart failure. Analogs of the incretin hormone glucagon-like peptide 1 (GLP-1) have shown some promise as cardioprotective agents. We hypothesized that a long-acting GLP-1 analog liraglutide would ameliorate cardiac remodeling over the course of 4 weeks in a rat model of non-reperfused myocardial infarction. In 134 male Sprague Dawley rats myocardial infarctions were induced by ligation of the left anterior descending coronary artery. Rats were randomized to either subcutaneous injection of placebo or 0.3. mg liraglutide once daily. Cardiac magnetic resonance imaging was performed after 4 weeks. Histology of the infarcted and remote non-infarcted myocardium, selected molecular remodeling markers and mitochondrial respiration in fibers of remote non-infarcted myocardium were analyzed. Left ventricular end diastolic volume increased in the infarcted hearts by 62% (from 0.58. ±. 0.03. mL to 0.95. ±. 0.07. mL, P. <. 0.05) compared to sham operated hearts and left ventricle ejection fraction decreased by 37% (63. ±. 1%-40. ±. 3%, P. <. 0.05). Increased interstitial fibrosis and phosphorylation of p38 Mitogen Activated Protein Kinase were observed in the non-infarct regions. Mitochondrial fatty acid oxidation was impaired. Liraglutide did not affect any of these alterations. Four-week treatment with liraglutide did not affect cardiac remodeling following a non-reperfused myocardial infarction, as assessed by cardiac magnetic resonance imaging, histological and molecular analysis and measurements of mitochondrial respiration.
KW - Acute myocardial infarction
KW - Cardiac magnetic resonance
KW - Cardiac remodeling
KW - GLP-1 receptor analog
KW - Heart failure
KW - Liraglutide
U2 - 10.1016/j.peptides.2017.04.009
DO - 10.1016/j.peptides.2017.04.009
M3 - Journal article
C2 - 28460895
AN - SCOPUS:85018879519
VL - 93
SP - 1
EP - 12
JO - Peptides
JF - Peptides
SN - 0196-9781
ER -