Special focus on the mitochondria in endothelial cells: A novel therapeutic target for gliflozins?

Gliflozins, also known as sodium-glucose cotransporter 2 inhibitors (SGLT2i), constitute a new class of antidiabetic drugs shown to reduce cardiovascular mortality and decrease hospitalisation frequency in patients with heart failure (HF), regardless of coexisting type 2 diabetes. In addition to lowering blood glucose levels by inhibiting renal glucose reabsorption, SGLT2i also affects sodium transport and improves cardiomyocyte mitochondrial function and energy metabolism. The influence of gliflozins on the metabolism and function of endothelial cells is not well understood. Endothelial dysfunction, which occurs in the single layer of cells lining the blood vessels, often precedes damage to heart muscle cells during HF. This dysfunction can manifest in two ways: 1) obstructive atherosclerosis in the coronary arteries due to subendothelial inflammation and lipid plaque deposition and 2) microvascular dysfunction stemming from structural and functional changes in smaller blood vessels. Both factors contribute to the progression of HF and reduce the amount of oxygen supplied to the myocardium. This review aimed to explore the latest findings from preclinical and clinical studies regarding the effects of gliflozins on endothelial cell function, mitochondrial activity and energy metabolism. Targeting endothelial injury may prove beneficial in preventing and treating both macro- and microcirculatory dysfunction, delaying heart failure progression and supporting cardiac regeneration. DATA AVAILABILITY: Data will be made available on request.