Myocardial protection from ischemia/reperfusion injury by exogenous galanin fragment.
OBJECTIVE
Galanin is a multifunctional neuropeptide with pleiotropic roles. The present study was designed to evaluate the potential effects of galanin (2-11) (G1) on functional and metabolic abnormalities in response to myocardial ischemia-reperfusion (I/R) injury.


METHODS
Peptide G1 was synthesized by the 9-fluorenylmethoxycarbonyl (Fmoc)-based solid-phase method. The chemical structure was identified by 1H-NMR spectroscopy and mass spectrometry. Experiments were conducted using a rat model of I/R injury in vivo, isolated perfused rat hearts ex vivo and cultured rat cardiomyoblast H9C2 cells in vitro. Cardiac function, infarct size, myocardial energy metabolism, hemodynamic parameters, plasma levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) were measured in order to evaluate the effects of G1 on myocardial I/R injury.


RESULTS
Treatment with G1 increased cell viability in a dose-dependent manner, inhibited cell apoptosis and excessive mitochondrial reactive oxygen species (ROS) production in response to oxidative stress in H9C2 cells. Pre- or postischemic infusion of G1 enhanced functional and metabolic recovery during reperfusion of the ischemic isolated rat heart. Administration of G1 at the onset of reperfusion significantly reduced infarct size and plasma levels of CK-MB and LDH in rats subjected to myocardial I/R injury.


CONCLUSIONS
These data provide the first evidence for cardioprotective activity of galanin G1 against myocardial I/R injury. Therefore, peptide G1 may represent a promising treatment strategy for ischemic heart disease.
National Institute of Health and Medical Research (INSERM), Toulouse, France.|University of Toulouse, UPS, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.
Andrei
A
Timotin
Russian Cardiology Research-and-Production Complex, Moscow, Russian Federation, Russia.
Oleg
O
Pisarenko
Russian Cardiology Research-and-Production Complex, Moscow, Russian Federation, Russia.
Maria
M
Sidorova
Russian Cardiology Research-and-Production Complex, Moscow, Russian Federation, Russia.
Irina
I
Studneva
Russian Cardiology Research-and-Production Complex, Moscow, Russian Federation, Russia.
Valentin
V
Shulzhenko
Russian Cardiology Research-and-Production Complex, Moscow, Russian Federation, Russia.
Marina
M
Palkeeva
Russian Cardiology Research-and-Production Complex, Moscow, Russian Federation, Russia.
Larisa
L
Serebryakova
Russian Cardiology Research-and-Production Complex, Moscow, Russian Federation, Russia.
Aleksander
A
Molokoedov
Russian Cardiology Research-and-Production Complex, Moscow, Russian Federation, Russia.
Oksana
O
Veselova
National Institute of Health and Medical Research (INSERM), Toulouse, France.|University of Toulouse, UPS, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.
Mathieu
M
Cinato
National Institute of Health and Medical Research (INSERM), Toulouse, France.|University of Toulouse, UPS, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.
Helene
H
Tronchere
National Institute of Health and Medical Research (INSERM), Toulouse, France.|University of Toulouse, UPS, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.
Frederic
F
Boal
National Institute of Health and Medical Research (INSERM), Toulouse, France.|University of Toulouse, UPS, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.
Oksana
O
Kunduzova
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D019004:Galanin / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D000067268:Isolated Heart Preparation; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar
D019004:Galanin
ROS production; energy metabolism; galanin (2-11); heart; ischemia and reperfusion