Lack of effect of prolonged treatment with liraglutide on cardiac remodeling in rats after acute myocardial infarction

Kasper Kyhl; Jacob Lønborg; Bolette Hartmann; Hannelouise Kissow; Steen Seier Poulsen; Henrik El Ali; Andreas Kjær; Flemming Dela; Thomas Engstrøm; Marek Treiman

doi:10.1016/j.peptides.2017.04.009

Lack of effect of prolonged treatment with liraglutide on cardiac remodeling in rats after acute myocardial infarction

Kasper Kyhl^*, Jacob Lønborg, Bolette Hartmann, Hannelouise Kissow, Steen Seier Poulsen, Henrik El Ali, Andreas Kjær, Flemming Dela, Thomas Engstrøm, Marek Treiman

^*Corresponding author af dette arbejde

9 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Peptides
Vol/bind	93
Sider (fra-til)	1-12
ISSN	0196-9781
DOI	https://doi.org/10.1016/j.peptides.2017.04.009
Status	Udgivet - jul. 2017

Adgang til dokumentet

10.1016/j.peptides.2017.04.009

Citationsformater

@article{d71f3771927c4670afe3143c8101f64e,

title = "Lack of effect of prolonged treatment with liraglutide on cardiac remodeling in rats after acute myocardial infarction",

abstract = "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.",

keywords = "Acute myocardial infarction, Cardiac magnetic resonance, Cardiac remodeling, GLP-1 receptor analog, Heart failure, Liraglutide",

author = "Kasper Kyhl and Jacob L{\o}nborg and Bolette Hartmann and Hannelouise Kissow and Poulsen, {Steen Seier} and Ali, {Henrik El} and Andreas Kj{\ae}r and Flemming Dela and Thomas Engstr{\o}m and Marek Treiman",

year = "2017",

month = jul,

doi = "10.1016/j.peptides.2017.04.009",

language = "English",

volume = "93",

pages = "1--12",

journal = "Peptides",

issn = "0196-9781",

publisher = "Elsevier",

}

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 - 2017/7

Y1 - 2017/7

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

SN - 0196-9781

VL - 93

SP - 1

EP - 12

JO - Peptides

JF - Peptides

ER -

Lack of effect of prolonged treatment with liraglutide on cardiac remodeling in rats after acute myocardial infarction

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater