Next Article in Journal
Prognostic Relevance of HJURP Expression in Patients with Surgically Resected Colorectal Cancer
Next Article in Special Issue
Deciphering the Role of Wnt and Rho Signaling Pathway in iPSC-Derived ARVC Cardiomyocytes by In Silico Mathematical Modeling
Previous Article in Journal
Optimizing the Profile of [99mTc]Tc–NT(7–13) Tracers in Pancreatic Cancer Models by Means of Protease Inhibitors
Previous Article in Special Issue
The Microenvironment of Decellularized Extracellular Matrix from Heart Failure Myocardium Alters the Balance between Angiogenic and Fibrotic Signals from Stromal Primitive Cells
 
 
Article

Statins Stimulate New Myocyte Formation After Myocardial Infarction by Activating Growth and Differentiation of the Endogenous Cardiac Stem Cells

1
Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy
2
Department of Experimental Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy
3
Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy
*
Authors to whom correspondence should be addressed.
These authors equally contribute to this study.
These authors share the seniorship for this study.
Int. J. Mol. Sci. 2020, 21(21), 7927; https://doi.org/10.3390/ijms21217927
Received: 25 September 2020 / Revised: 21 October 2020 / Accepted: 22 October 2020 / Published: 26 October 2020
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. View Full-Text
Keywords: Statins; 3-hydroxy-3-methylglutaryl coenzyme A; cardiac stem cells; myocardial regeneration; Akt Statins; 3-hydroxy-3-methylglutaryl coenzyme A; cardiac stem cells; myocardial regeneration; Akt
Show Figures

Figure 1

MDPI and ACS Style

Cianflone, E.; Cappetta, D.; Mancuso, T.; Sabatino, J.; Marino, F.; Scalise, M.; Albanese, M.; Salatino, A.; Parrotta, E.I.; Cuda, G.; De Angelis, A.; Berrino, L.; Rossi, F.; Nadal-Ginard, B.; Torella, D.; Urbanek, K. Statins Stimulate New Myocyte Formation After Myocardial Infarction by Activating Growth and Differentiation of the Endogenous Cardiac Stem Cells. Int. J. Mol. Sci. 2020, 21, 7927. https://doi.org/10.3390/ijms21217927

AMA Style

Cianflone E, Cappetta D, Mancuso T, Sabatino J, Marino F, Scalise M, Albanese M, Salatino A, Parrotta EI, Cuda G, De Angelis A, Berrino L, Rossi F, Nadal-Ginard B, Torella D, Urbanek K. Statins Stimulate New Myocyte Formation After Myocardial Infarction by Activating Growth and Differentiation of the Endogenous Cardiac Stem Cells. International Journal of Molecular Sciences. 2020; 21(21):7927. https://doi.org/10.3390/ijms21217927

Chicago/Turabian Style

Cianflone, Eleonora, Donato Cappetta, Teresa Mancuso, Jolanda Sabatino, Fabiola Marino, Mariangela Scalise, Michele Albanese, Alessandro Salatino, Elvira Immacolata Parrotta, Giovanni Cuda, Antonella De Angelis, Liberato Berrino, Francesco Rossi, Bernardo Nadal-Ginard, Daniele Torella, and Konrad Urbanek. 2020. "Statins Stimulate New Myocyte Formation After Myocardial Infarction by Activating Growth and Differentiation of the Endogenous Cardiac Stem Cells" International Journal of Molecular Sciences 21, no. 21: 7927. https://doi.org/10.3390/ijms21217927

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop