Cardioprotective Mechanisms of SGLT2 Inhibitors Against Cancer Treatment–Induced CardiotoxicitySodium-glucose cotransporter-2 (SGLT2) inhibitors protect against cardiovascular toxicity induced by anticancer drugs via multiple mechanisms

Cardioprotective Mechanisms of SGLT2 Inhibitors Against Cancer Treatment–Induced CardiotoxicitySodium-glucose cotransporter-2 (SGLT2) inhibitors protect against cardiovascular toxicity induced by anticancer drugs via multiple mechanisms. They enhance energy metabolism by increasing the activation of nutrient deprivation pathways (adenosine monophosphate-activated protein kinase [AMPK] and sirtuin [SIRT] 1, SIRT3, and SIRT6) while inhibiting the nutrient surplus pathways (AKT/mammalian target of rapamycin [mTOR]), resulting in enhanced autophagy and increased mitochondrial biogenesis (peroxisome proliferator–activated receptor-γ coactivator-1α [PGC-1α]). Additionally, SGLT2 inhibitors mitigate oxidative and endoplasmic reticulum (ER) stress, block inflammatory pathways, inhibit ferroptosis, and enhance ketogenesis. Created using BioRender.com. ATF-4 = activating transcription factor 4; CHOP = C/EBP homologous protein; eIF-2α = eukaryotic initiation factor 2α; Ho-1 = heme oxygenase 1; MDA = malondialdehyde; MMP = matrix metalloproteinase; NLRP-3 = nod-like receptor pyrin domain containing 3; NF-κB = nuclear factor κB; NOX-1 = NADPH oxidase 1; NOX-2 = NADPH oxidase 2; Nrf-2 = nuclear factor erythroid 2–related factor 2; NQO1 = NAD(P)H quinone dehydrogenase 1; PERK = protein kinase R-like endoplasmic reticulum kinase; ROS = reactive oxygen species; SOD = superoxide dismutase; TNF = tumor necrosis factor

Publication

The Cardioprotective and Anticancer Effects of SGLT2 Inhibitors (2024) Mohamed S. Dabour, et al. JACC CardioOncol. 2024 Apr;6(2). Figure: F1. Homo sapiens

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