Cardioprotective effects of lixisenatide in rat myocardial ischemia-reperfusion injury studies.

Wohlfart P, Linz W, Hübschle T, Linz D, Huber J, Hess S, Crowther D, Werner U, Ruetten H

Journal of translational medicine28 Mar 2013Cited by 62 (Europe PMC)

PMID23537041PMCIDPMC3637243DOI10.1186/1479-5876-11-84PepBankPUB-23537041

Summary

BackgroundLixisenatide is a glucagon-like peptide-1 analog which stimulates insulin secretion and inhibits glucagon secretion and gastric emptying. We investigated cardioprotective effects of lixisenatide in rodent models reflecting the clinical situation.MethodsThe acute cardiac effects of lixisenatide were investigated in isolated rat hearts subjected to brief ischemia and reperfusion. Effects of chronic treatment with lixisenatide on cardiac function were assessed in a modified rat heart failure model after only transient coronary occlusion followed by long-term reperfusion. Freshly isolated cardiomyocytes were used to investigate cell-type specific mechanisms of lixisenatide action.ResultsIn the acute setting of ischemia-reperfusion, lixisenatide reduced the infarct-size/area at risk by 36% ratio without changes on coronary flow, left-ventricular pressure and heart rate. Treatment with lixisenatide for 10 weeks, starting after cardiac ischemia and reperfusion, improved left ventricular end-diastolic pressure and relaxation time and prevented lung congestion in comparison to placebo. No anti-fibrotic effect was observed. Gene expression analysis revealed a change in remodeling genes comparable to the ACE inhibitor ramipril. In isolated cardiomyocytes lixisenatide reduced apoptosis and increased fractional shortening. Glucagon-like peptide-1 receptor (GLP1R) mRNA expression could not be detected in rat heart samples or isolated cardiomyocytes. Surprisingly, cardiomyocytes isolated from GLP-1 receptor knockout mice still responded to lixisenatide.ConclusionsIn rodent models, lixisenatide reduced in an acute setting infarct-size and improved cardiac function when administered long-term after ischemia-reperfusion injury. GLP-1 receptor independent mechanisms contribute to the described cardioprotective effect of lixisenatide. Based in part on these preclinical findings patients with cardiac dysfunction are currently being recruited for a randomized, double-blind, placebo-controlled, multicenter study with lixisenatide.Trial registration(ELIXA, ClinicalTrials.gov Identifier: NCT01147250).

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study10

10 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In rats after cardiac ischemia-reperfusion, lixisenatide improved left ventricular end-diastolic pressure versus placebo.
In plain wordsIn rats after heart injury, lixisenatide improved ventricular filling pressure compared with placebo.
Peptide
Lixisenatide
Outcome
Direction not reportedLeft ventricular end-diastolic pressure
Study
ratn: not reported in source
Myocardial ischemia-reperfusion injury
Comparator
Placebo
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated · 10 weeksAs given in this study (rat).
Source sentences
Summary
Treatment with lixisenatide for 10 weeks, starting after cardiac ischemia and reperfusion, improved left ventricular end-diastolic pressure and relaxation time and prevented lung congestion in comparison to placebo.
1 context sentence(design, population, supporting numbers)
Summary · context
Effects of chronic treatment with lixisenatide on cardiac function were assessed in a modified rat heart failure model after only transient coronary occlusion followed by long-term reperfusion.
Show in the study text Report a problemFND-2353704103
02AnimalAnimal study (in vivo)Efficacy outcome
In rats after cardiac ischemia-reperfusion, lixisenatide improved cardiac relaxation time versus placebo.
In plain wordsIn rats after heart injury, lixisenatide improved heart relaxation time compared with placebo.
Peptide
Lixisenatide
Outcome
Direction not reportedRelaxation time
Study
ratn: not reported in source
Myocardial ischemia-reperfusion injury
Comparator
Placebo
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated · 10 weeksAs given in this study (rat).
Source sentences
Summary
Treatment with lixisenatide for 10 weeks, starting after cardiac ischemia and reperfusion, improved left ventricular end-diastolic pressure and relaxation time and prevented lung congestion in comparison to placebo.
1 context sentence(design, population, supporting numbers)
Summary · context
Effects of chronic treatment with lixisenatide on cardiac function were assessed in a modified rat heart failure model after only transient coronary occlusion followed by long-term reperfusion.
Show in the study text Report a problemFND-2353704104
03AnimalAnimal study (in vivo)Efficacy outcome
In rats after cardiac ischemia-reperfusion, lixisenatide prevented lung congestion compared with placebo.
In plain wordsIn rats after heart injury, lixisenatide prevented lung congestion compared with placebo.
Peptide
Lixisenatide
Outcome
DecreaseLung congestion
Study
ratn: not reported in source
Myocardial ischemia-reperfusion injury
Comparator
Placebo
Outcome group
Heart function · Respiratory
Studied dose
Dose not stated · 10 weeksAs given in this study (rat).
Source sentences
Summary
Treatment with lixisenatide for 10 weeks, starting after cardiac ischemia and reperfusion, improved left ventricular end-diastolic pressure and relaxation time and prevented lung congestion in comparison to placebo.
1 context sentence(design, population, supporting numbers)
Summary · context
Effects of chronic treatment with lixisenatide on cardiac function were assessed in a modified rat heart failure model after only transient coronary occlusion followed by long-term reperfusion.
Show in the study text Report a problemFND-2353704105
04AnimalAnimal study (in vivo)Efficacy outcome
In rat cardiac injury studies, no anti-fibrotic effect of lixisenatide was observed.
In plain wordsIn rats with heart injury, lixisenatide had no observed effect against fibrosis.
Peptide
Lixisenatide
Outcome
Direction not reportedFibrosis
Study
ratn: not reported in source
Myocardial ischemia-reperfusion injury
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
No anti-fibrotic effect was observed.
1 context sentence(design, population, supporting numbers)
Summary · context
Effects of chronic treatment with lixisenatide on cardiac function were assessed in a modified rat heart failure model after only transient coronary occlusion followed by long-term reperfusion.
Show in the study text Report a problemFND-2353704106
05AnimalAnimal study (in vivo)Mechanism
In rat cardiac injury studies, lixisenatide changed remodeling gene expression comparably to ramipril.
In plain wordsIn rats with heart injury, lixisenatide changed remodeling genes similarly to ramipril.
Peptide
Lixisenatide
Outcome
Direction not reportedRemodeling gene expression
Study
ratn: not reported in source
Myocardial ischemia-reperfusion injury
Comparator
Ramipril
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Gene expression analysis revealed a change in remodeling genes comparable to the ACE inhibitor ramipril.
1 context sentence(design, population, supporting numbers)
Summary · context
Effects of chronic treatment with lixisenatide on cardiac function were assessed in a modified rat heart failure model after only transient coronary occlusion followed by long-term reperfusion.
Show in the study text Report a problemFND-2353704107
06LabEx vivo tissueEfficacy outcome
In isolated rat hearts after ischemia-reperfusion, lixisenatide reduced the infarct-size/area-at-risk ratio by 36%.
In plain wordsIn lab tests with rat hearts, lixisenatide reduced the relative infarct size.
Peptide
Lixisenatide
Outcome
DecreaseInfarct-size/area-at-risk ratio
Study
ratn: not reported in source
Myocardial ischemia-reperfusion injury
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
In the acute setting of ischemia-reperfusion, lixisenatide reduced the infarct-size/area at risk by 36% ratio without changes on coronary flow, left-ventricular pressure and heart rate.
1 context sentence(design, population, supporting numbers)
Summary · context
The acute cardiac effects of lixisenatide were investigated in isolated rat hearts subjected to brief ischemia and reperfusion.
Show in the study text Report a problemFND-2353704101
07LabEx vivo tissueEfficacy outcome
In isolated rat hearts after ischemia-reperfusion, lixisenatide did not change coronary flow, left-ventricular pressure or heart rate.
In plain wordsIn lab tests with rat hearts, lixisenatide did not change coronary flow, ventricular pressure or heart rate.
Peptide
Lixisenatide
Outcome
Direction not reportedAcute cardiac hemodynamics
Study
ratn: not reported in source
Myocardial ischemia-reperfusion injury
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
In the acute setting of ischemia-reperfusion, lixisenatide reduced the infarct-size/area at risk by 36% ratio without changes on coronary flow, left-ventricular pressure and heart rate.
1 context sentence(design, population, supporting numbers)
Summary · context
The acute cardiac effects of lixisenatide were investigated in isolated rat hearts subjected to brief ischemia and reperfusion.
Show in the study text Report a problemFND-2353704102
08LabIn vitro (cells)Mechanism
In isolated rat cardiomyocytes, lixisenatide reduced apoptosis.
In plain wordsIn lab tests with rat heart cells, lixisenatide reduced programmed cell death.
Peptide
Lixisenatide
Outcome
DecreaseApoptosis
Study
ratn: not reported in source
Isolated cardiomyocytes
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
In isolated cardiomyocytes lixisenatide reduced apoptosis and increased fractional shortening.
1 context sentence(design, population, supporting numbers)
Summary · context
Freshly isolated cardiomyocytes were used to investigate cell-type specific mechanisms of lixisenatide action.
Show in the study text Report a problemFND-2353704108
09LabIn vitro (cells)Activity measurement
In isolated rat cardiomyocytes, lixisenatide increased fractional shortening.
In plain wordsIn lab tests with rat heart cells, lixisenatide increased fractional shortening.
Peptide
Lixisenatide
Outcome
IncreaseFractional shortening
Study
ratn: not reported in source
Isolated cardiomyocytes
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
In isolated cardiomyocytes lixisenatide reduced apoptosis and increased fractional shortening.
1 context sentence(design, population, supporting numbers)
Summary · context
Freshly isolated cardiomyocytes were used to investigate cell-type specific mechanisms of lixisenatide action.
Show in the study text Report a problemFND-2353704109
10LabIn vitro (cells)Mechanism
In cardiomyocytes from GLP-1 receptor knockout mice, responses to lixisenatide remained present.
In plain wordsIn lab tests with cells from mice lacking the GLP-1 receptor, lixisenatide still produced a response.
Peptide
Lixisenatide
Outcome
Direction not reportedResponse without GLP-1 receptor
Study
micen: not reported in source
Cardiomyocytes from GLP-1 receptor knockout mice
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Surprisingly, cardiomyocytes isolated from GLP-1 receptor knockout mice still responded to lixisenatide.
Show in the study text Report a problemFND-2353704110

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT01147250

Evaluation of Cardiovascular Outcomes in Patients With Type 2 Diabetes After Acute Coronary Syndrome During Treatment With AVE0010 (Lixisenatide)

Sanofin = 6,068Jun 2010 to Feb 2015

Acute Coronary Syndrome

Trial page ClinicalTrials.govUpdated 20 Dec 2016

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:36 UTC
First added · source update from Europe PMC

PepBank is a research reference. Talk to a doctor before you use any peptide.