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Article

Combined Therapy with Simvastatin- and Coenzyme-Q10-Loaded Nanoparticles Upregulates the Akt-eNOS Pathway in Experimental Metabolic Syndrome

by
Ezgi Şaman
1,
Martina Cebova
1,
Andrej Barta
1,
Martina Koneracka
2,
Vlasta Zavisova
2,
Anita Eckstein-Andicsova
3,
Martin Danko
3,
Jaroslav Mosnacek
3,4 and
Olga Pechanova
1,5,*
1
Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, 813 71 Bratislava, Slovakia
2
Institute of Experimental Physics, Slovak Academy of Sciences, 040 01 Kosice, Slovakia
3
Polymer Institute, Slovak Academy of Sciences, 845 41 Bratislava, Slovakia
4
Centre for Advanced Materials Application, 845 11 Bratislava, Slovakia
5
Institute of Pathophysiology, Faculty of Medicine, Comenius University, 811 08 Bratislava, Slovakia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(1), 276; https://doi.org/10.3390/ijms24010276
Submission received: 15 November 2022 / Revised: 17 December 2022 / Accepted: 20 December 2022 / Published: 23 December 2022
(This article belongs to the Special Issue Biopolymers as Nanoparticles Carriers)
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Abstract

In addition to their LDL-cholesterol-lowering effect, statins have pleiotropic beneficial effects on the cardiovascular system. However, long-term treatment with statins may be associated with serious side effects. With the aim to make statin therapy more effective, we studied the effects of simvastatin- and coenzyme-Q10-loaded polymeric nanoparticles on the lipid profile and nitric oxide (NO)/reactive oxygen species (ROS) balance in the heart and aorta of adult male obese Zucker rats. The rats were divided into an untreated group, a group treated with empty nanoparticles, and groups treated with simvastatin-, coenzyme Q10 (CoQ10)-, or a combination of simvastatin- and CoQ10-loaded nanoparticles (SIMV+CoQ10). After 6 weeks, the lipid profile in the plasma and the concentration of conjugated dienes in the liver were determined. Nitric oxide synthase (NOS) activity, Akt, endothelial NOS (eNOS), phosphorylated eNOS (p-eNOS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and nuclear factor kappaB (NF-kappaB) protein expressions were measured in the heart and aorta. All simvastatin, CoQ10, and SIMV+CoQ10 treatments decreased plasma LDL levels, but only the combined SIMV+CoQ10 treatment increased NOS activity and the expression of Akt, eNOS, and p-eNOS in both the heart and the aorta. Interestingly, NADPH oxidase in the heart and NF-kappaB protein expression in the aorta were decreased by all treatments, including nanoparticles alone. In conclusion, only combined therapy with SIMV- and CoQ10-loaded nanoparticles increased NOS activity and upregulated the Akt-eNOS pathway in obese Zucker rats, which may represent a promising tool for the treatment of cardiometabolic diseases.
Keywords: statins; polymeric nanoparticles; nitric oxide synthase; Akt-eNOS pathway; nicotinamide adenine dinucleotide phosphate oxidase; nuclear factor kappaB; cardiometabolic diseases statins; polymeric nanoparticles; nitric oxide synthase; Akt-eNOS pathway; nicotinamide adenine dinucleotide phosphate oxidase; nuclear factor kappaB; cardiometabolic diseases
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MDPI and ACS Style

Şaman, E.; Cebova, M.; Barta, A.; Koneracka, M.; Zavisova, V.; Eckstein-Andicsova, A.; Danko, M.; Mosnacek, J.; Pechanova, O. Combined Therapy with Simvastatin- and Coenzyme-Q10-Loaded Nanoparticles Upregulates the Akt-eNOS Pathway in Experimental Metabolic Syndrome. Int. J. Mol. Sci. 2023, 24, 276. https://doi.org/10.3390/ijms24010276

AMA Style

Şaman E, Cebova M, Barta A, Koneracka M, Zavisova V, Eckstein-Andicsova A, Danko M, Mosnacek J, Pechanova O. Combined Therapy with Simvastatin- and Coenzyme-Q10-Loaded Nanoparticles Upregulates the Akt-eNOS Pathway in Experimental Metabolic Syndrome. International Journal of Molecular Sciences. 2023; 24(1):276. https://doi.org/10.3390/ijms24010276

Chicago/Turabian Style

Şaman, Ezgi, Martina Cebova, Andrej Barta, Martina Koneracka, Vlasta Zavisova, Anita Eckstein-Andicsova, Martin Danko, Jaroslav Mosnacek, and Olga Pechanova. 2023. "Combined Therapy with Simvastatin- and Coenzyme-Q10-Loaded Nanoparticles Upregulates the Akt-eNOS Pathway in Experimental Metabolic Syndrome" International Journal of Molecular Sciences 24, no. 1: 276. https://doi.org/10.3390/ijms24010276

APA Style

Şaman, E., Cebova, M., Barta, A., Koneracka, M., Zavisova, V., Eckstein-Andicsova, A., Danko, M., Mosnacek, J., & Pechanova, O. (2023). Combined Therapy with Simvastatin- and Coenzyme-Q10-Loaded Nanoparticles Upregulates the Akt-eNOS Pathway in Experimental Metabolic Syndrome. International Journal of Molecular Sciences, 24(1), 276. https://doi.org/10.3390/ijms24010276

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