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Evaluation of anti-atherosclerotic effects of Sitagliptin via modulation of the mTOR pathway in male rabbits

Atherosclerosis is a common and serious vascular disease that underlies many cardiovascular and cerebrovascular illnesses, including heart attack and stroke. Atherosclerosis-related illnesses have increased in prevalence and now pose a substantial burden on individuals and society. Autophagy (AP) is...

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Detalles Bibliográficos
Autores principales: Sahib, Hussam Hamza, Mohammad, Bassim, Hadi, Najah Rayish
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Carol Davila University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10165524/
https://www.ncbi.nlm.nih.gov/pubmed/37168300
http://dx.doi.org/10.25122/jml-2022-0298
Descripción
Sumario:Atherosclerosis is a common and serious vascular disease that underlies many cardiovascular and cerebrovascular illnesses, including heart attack and stroke. Atherosclerosis-related illnesses have increased in prevalence and now pose a substantial burden on individuals and society. Autophagy (AP) is a process in which cytoplasmic components are engulfed by a double-membrane structure, such as defective organelles and aged, damaged, and flawed proteins. Autophagy is essential for maintaining a proper cellular equilibrium and plays a vital homeostatic role in physiological settings by liberating nutrients from macromolecules and removing undesirable cellular components. This study aimed to investigate the effect of Sitagliptin on the progression of atherosclerosis. Twenty-one male New Zealand White rabbits weighing 2-2.5 kg each were split into three groups: normal control, atherogenic control, and Sitagliptin-treated. The following parameters: serum triglycerides (TG), total cholesterol (TC), LDL, and a tissue autophagy marker (p62) using ELISA, aortic mRNA expression of mTORC1 marker using Real-Time Quantitative PCR(RT-qPCR), and histological inspection of the aorta were assessed. The mRNA expression of mTORC1 and the lipid profile of aortic tissue are considerably elevated in atherogenic diet-fed animals. Histopathological analysis confirmed the presence of a substantial atherosclerotic lesion in the animals fed an atherogenic diet. However, compared to an atherogenic control group, Sitagliptin dramatically reduced lipid profile, P62 aortic level, and mRNA expression of mTORC1. Sitagliptin medication slowed the development of atherosclerosis via increasing autophagy through suppression of the mTORC1 signaling pathway.