CELLULAR AND MITOCHONDRIAL PATHWAYS CONTRIBUTE TO SGLT2i-MEDIATED TISSUE PROTECTION: EXPERIMENTAL AND CLINICAL DATA

RAÚL SANZ; SEBASTÁN GARCÍA MENÉNDEZ; FELIPE INSERRA; LEÓN FERDER; WALTER MANUCHA

CURRENT PHARMACEUTICAL DESIGN.

BENTHAM SCIENCE PUBL LTD

Lugar: Oak Park; Año: 2024 vol. 30 p. 969 - 974

1381-6128

Cardiovascular disease is prevalent among people with metabolic syndrome and diabetes, where mitochondrial dysfunction is a significant player in its development and persistence, including remodeling and consequent cardiac events. In this context, angiotensin II - the main interlocutor of the renin-angiotensin-aldosterone system - promotes local and systemic oxidative inflammatory processes. To highlight, the low activity/expression of proteins called sirtuins negatively participates in these processes, allowing more significant oxidative imbalance, which impacts cellular and tissue responses, causing tissue damage, inflammation, and cardiac and vascular remodeling. The reduction in energy production of mitochondria has been widely described as a significant element in all types of metabolic disorders. Additionally, high sirtuin levels, and AMPK signaling stimulates HIF-1 beta and promotes ketosis. All these effects favor autophagy and mitophagy, clean cardiac cells with damaged organelles, and reduce oxidative stress and the inflammatory response, protecting cardiac tissue. In this sense and of particular interest, SGLT2 inhibitors profoundly influence all these mechanisms. To highlight, recent randomized clinical trials that included SGLT2 inhibitors have shown impressive results in improving cardiac function and reducing cardiovascular and renal events. Furthermore, recent evidence shows that SLGT2 inhibitors mimic this protective process, improving mitochondrial function, oxidative stress, and inflammation. Finally, regarding the protection described above at the cardiovascular level, it is necessary to deepen the knowledge of the effects of SGLT2 inhibitors on mitochondrial function.