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Statins Stimulate New Myocyte Formation After Myocardial Infarction by Activating Growth and Differentiation of the Endogenous Cardiac Stem Cells
by
Mancuso, Teresa
, Sabatino, Jolanda
, Scalise, Mariangela
, Urbanek, Konrad
, Berrino, Liberato
, De Angelis, Antonella
, Rossi, Francesco
, Nadal-Ginard, Bernardo
, Cappetta, Donato
, Cuda, Giovanni
, Albanese, Michele
, Torella, Daniele
, Salatino, Alessandro
, Marino, Fabiola
, Parrotta, Elvira Immacolata
, Cianflone, Eleonora
in
Animals
/ Apoptosis
/ Cardiomyocytes
/ Cell cycle
/ Cell Differentiation - drug effects
/ Cell growth
/ Cell Proliferation - drug effects
/ Cells, Cultured
/ Cloning
/ Disease Models, Animal
/ Drinking water
/ Female
/ Heart attacks
/ Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage
/ Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology
/ Kinases
/ Mice
/ Muscle Cells - cytology
/ Muscle Cells - drug effects
/ Muscle Cells - metabolism
/ Myocardial Infarction - drug therapy
/ Myocardial Infarction - etiology
/ Myocardial Infarction - metabolism
/ Myocardium - cytology
/ Myocardium - metabolism
/ Phosphorylation
/ Phosphorylation - drug effects
/ Pravastatin - administration & dosage
/ Pravastatin - pharmacology
/ Proto-Oncogene Proteins c-akt - metabolism
/ Rats
/ Rosuvastatin Calcium - administration & dosage
/ Rosuvastatin Calcium - pharmacology
/ Simvastatin - administration & dosage
/ Simvastatin - pharmacology
/ Statins
/ Stem cells
/ Stem Cells - cytology
/ Stem Cells - drug effects
/ Stem Cells - metabolism
2020
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Statins Stimulate New Myocyte Formation After Myocardial Infarction by Activating Growth and Differentiation of the Endogenous Cardiac Stem Cells
by
Mancuso, Teresa
, Sabatino, Jolanda
, Scalise, Mariangela
, Urbanek, Konrad
, Berrino, Liberato
, De Angelis, Antonella
, Rossi, Francesco
, Nadal-Ginard, Bernardo
, Cappetta, Donato
, Cuda, Giovanni
, Albanese, Michele
, Torella, Daniele
, Salatino, Alessandro
, Marino, Fabiola
, Parrotta, Elvira Immacolata
, Cianflone, Eleonora
in
Animals
/ Apoptosis
/ Cardiomyocytes
/ Cell cycle
/ Cell Differentiation - drug effects
/ Cell growth
/ Cell Proliferation - drug effects
/ Cells, Cultured
/ Cloning
/ Disease Models, Animal
/ Drinking water
/ Female
/ Heart attacks
/ Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage
/ Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology
/ Kinases
/ Mice
/ Muscle Cells - cytology
/ Muscle Cells - drug effects
/ Muscle Cells - metabolism
/ Myocardial Infarction - drug therapy
/ Myocardial Infarction - etiology
/ Myocardial Infarction - metabolism
/ Myocardium - cytology
/ Myocardium - metabolism
/ Phosphorylation
/ Phosphorylation - drug effects
/ Pravastatin - administration & dosage
/ Pravastatin - pharmacology
/ Proto-Oncogene Proteins c-akt - metabolism
/ Rats
/ Rosuvastatin Calcium - administration & dosage
/ Rosuvastatin Calcium - pharmacology
/ Simvastatin - administration & dosage
/ Simvastatin - pharmacology
/ Statins
/ Stem cells
/ Stem Cells - cytology
/ Stem Cells - drug effects
/ Stem Cells - metabolism
2020
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Statins Stimulate New Myocyte Formation After Myocardial Infarction by Activating Growth and Differentiation of the Endogenous Cardiac Stem Cells
by
Mancuso, Teresa
, Sabatino, Jolanda
, Scalise, Mariangela
, Urbanek, Konrad
, Berrino, Liberato
, De Angelis, Antonella
, Rossi, Francesco
, Nadal-Ginard, Bernardo
, Cappetta, Donato
, Cuda, Giovanni
, Albanese, Michele
, Torella, Daniele
, Salatino, Alessandro
, Marino, Fabiola
, Parrotta, Elvira Immacolata
, Cianflone, Eleonora
in
Animals
/ Apoptosis
/ Cardiomyocytes
/ Cell cycle
/ Cell Differentiation - drug effects
/ Cell growth
/ Cell Proliferation - drug effects
/ Cells, Cultured
/ Cloning
/ Disease Models, Animal
/ Drinking water
/ Female
/ Heart attacks
/ Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage
/ Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology
/ Kinases
/ Mice
/ Muscle Cells - cytology
/ Muscle Cells - drug effects
/ Muscle Cells - metabolism
/ Myocardial Infarction - drug therapy
/ Myocardial Infarction - etiology
/ Myocardial Infarction - metabolism
/ Myocardium - cytology
/ Myocardium - metabolism
/ Phosphorylation
/ Phosphorylation - drug effects
/ Pravastatin - administration & dosage
/ Pravastatin - pharmacology
/ Proto-Oncogene Proteins c-akt - metabolism
/ Rats
/ Rosuvastatin Calcium - administration & dosage
/ Rosuvastatin Calcium - pharmacology
/ Simvastatin - administration & dosage
/ Simvastatin - pharmacology
/ Statins
/ Stem cells
/ Stem Cells - cytology
/ Stem Cells - drug effects
/ Stem Cells - metabolism
2020
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Statins Stimulate New Myocyte Formation After Myocardial Infarction by Activating Growth and Differentiation of the Endogenous Cardiac Stem Cells
Journal Article
Statins Stimulate New Myocyte Formation After Myocardial Infarction by Activating Growth and Differentiation of the Endogenous Cardiac Stem Cells
2020
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Overview
The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) exert pleiotropic effects on cardiac cell biology which are not yet fully understood. Here we tested whether statin treatment affects resident endogenous cardiac stem/progenitor cell (CSC) activation in vitro and in vivo after myocardial infarction (MI). Statins (Rosuvastatin, Simvastatin and Pravastatin) significantly increased CSC expansion in vitro as measured by both BrdU incorporation and cell growth curve. Additionally, statins increased CSC clonal expansion and cardiosphere formation. The effects of statins on CSC growth and differentiation depended on Akt phosphorylation. Twenty-eight days after myocardial infarction by permanent coronary ligation in rats, the number of endogenous CSCs in the infarct border zone was significantly increased by Rosuvastatin-treatment as compared to untreated controls. Additionally, commitment of the activated CSCs into the myogenic lineage (c-kitpos/Gata4pos CSCs) was increased by Rosuvastatin administration. Accordingly, Rosuvastatin fostered new cardiomyocyte formation after MI. Finally, Rosuvastatin treatment reversed the cardiomyogenic defects of CSCs in c-kit haploinsufficient mice, increasing new cardiomyocyte formation by endogenous CSCs in these mice after myocardial infarction. In summary, statins, by sustaining Akt activation, foster CSC growth and differentiation in vitro and in vivo. The activation and differentiation of the endogenous CSC pool and consequent new myocyte formation by statins improve myocardial remodeling after coronary occlusion in rodents. Similar effects might contribute to the beneficial effects of statins on human cardiovascular diseases.
Publisher
MDPI AG,MDPI
Subject
/ Cell Differentiation - drug effects
/ Cell Proliferation - drug effects
/ Cloning
/ Female
/ Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage
/ Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology
/ Kinases
/ Mice
/ Myocardial Infarction - drug therapy
/ Myocardial Infarction - etiology
/ Myocardial Infarction - metabolism
/ Phosphorylation - drug effects
/ Pravastatin - administration & dosage
/ Proto-Oncogene Proteins c-akt - metabolism
/ Rats
/ Rosuvastatin Calcium - administration & dosage
/ Rosuvastatin Calcium - pharmacology
/ Simvastatin - administration & dosage
/ Statins
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