Effect of Atorvastatin on Angiogenesis-Related Genes VEGF-A, HGF and IGF-1 and the Modulation of PI3K/AKT/mTOR Transcripts in Bone-Marrow-Derived Mesenchymal Stem Cells

Adriana Adamičková; Nikola Chomaničová; Andrea Gažová; Juraj Maďarič; Zdenko Červenák; Simona Valášková; Matúš Adamička; Jan Kyselovic

doi:10.3390/cimb45030150

Effect of Atorvastatin on Angiogenesis-Related Genes VEGF-A, HGF and IGF-1 and the Modulation of PI3K/AKT/mTOR Transcripts in Bone-Marrow-Derived Mesenchymal Stem Cells

Curr Issues Mol Biol. 2023 Mar 10;45(3):2326-2337. doi: 10.3390/cimb45030150.

Authors

Adriana Adamičková¹, Nikola Chomaničová¹, Andrea Gažová², Juraj Maďarič³, Zdenko Červenák¹, Simona Valášková¹, Matúš Adamička⁴, Jan Kyselovic^{1

5}

Affiliations

¹ 5th Department of Internal Medicine, Faculty of Medicine, Comenius University Bratislava, 813 72 Bratislava, Slovakia.
² Institute of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Comenius University Bratislava, 813 72 Bratislava, Slovakia.
³ Clinic of Angiology, Comenius University and National Institute of Cardiovascular Diseases, 833 48 Bratislava, Slovakia.
⁴ Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University Bratislava, 813 72 Bratislava, Slovakia.
⁵ Department of Pharmacology and Toxicology, University of Veterinary Medicine and Pharmacy in Kosice, 041 81 Kosice, Slovakia.

Abstract

Stem cell transplantation represents a unique therapeutic tool in tissue engineering and regenerative medicine. However, it was shown that the post-injection survival of stem cells is poor, warranting a more comprehensive understanding of activated regenerative pathways. Numerous studies indicate that statins improve the therapeutic efficacy of stem cells in regenerative medicine. In the present study, we investigated the effect of the most widely prescribed statin, atorvastatin, on the characteristics and properties of bone-marrow-derived mesenchymal stem cells (BM-MSCs) cultured in vitro. We found that atorvastatin did not decrease the viability of BM-MSCs, nor did it change the expression of MSC cell surface markers. Atorvastatin upregulated the mRNA expression levels of VEGF-A and HGF, whereas the mRNA expression level of IGF-1 was decreased. In addition, the PI3K/AKT signaling pathway was modulated by atorvastatin as indicated by the high mRNA expression levels of PI3K and AKT. Moreover, our data revealed the upregulation of mTOR mRNA levels; however, no change was observed in the BAX and BCL-2 transcripts. We propose that atorvastatin benefits BM-MSC treatment due to its ability to upregulate angiogenesis-related genes expression and transcripts of the PI3K/AKT/mTOR pathway.

Keywords: bone-marrow-derived mesenchymal stem cells; growth factors; paracrine factors; regenerative therapy; statins.

Grants and funding

This research was funded by a grant from the Ministry of the Health of the Slovak Republic 2016/13-FAUK-1. This article was created thanks to support under the Operational Program Integrated Infrastructure for the project: National infrastructure for supporting technology transfer in Slovakia II–NITT SK II, co-financed by the European Regional Development Fund. This publication was created thanks to support within the Operational Program Integrated Infrastructure for the project: Increasing the capacities and competencies of the Comenius University in research, development and innovation 313021BUZ3, co-financed from the resources of the European Regional Development Fund.