Key result
SGLT2 inhibitors attenuate endothelial and microvascular dysfunction via multiple mechanisms, contributing to their beneficial cardiovascular effects.
Why the study?
Although the beneficial cardiovascular effects of SGLT2 inhibitors are well established, the exact underlying mechanisms remain largely unknown.
Do SGLT2 inhibitors improve endothelial function and microcirculation?
Do SGLT2 inhibitors improve endothelial function and microcirculation?
This review highlights that the cardiovascular benefits of SGLT2 inhibitors may be partly driven by direct improvements in endothelial and microvascular function.
May partly explain SGLT2i CV benefits via endothelial effects; leaves open confirmation in dedicated microvascular RCTs.
AIMS: The beneficial cardiovascular effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors irrespective of the presence of diabetes mellitus are nowadays well established and they already constitute a significant pillar for the management of heart failure, irrespective of the ejection fraction. The exact underlying mechanisms accountable for these effects, however, remain largely unknown. The direct effect on endothelial function and microcirculation is one of the most well studied. The broad range of studies presented in this review aims to link all available data from the bench to bedside and highlight the existing gaps as well as the future directions in the investigations concerning the effects of SGLT2 inhibitors on the endothelium and the microcirculation. METHODS AND RESULTS: An extensive search has been conducted using the MEDLINE/PubMed database in order to identify the relevant studies. Preclinical data suggest that SGLT2 inhibitors directly affect endothelial function independently of glucose and specifically via several interplaying molecular pathways, resulting in improved vasodilation, increased NO production, enhanced mitochondrial homeostasis, endothelial cell viability, and angiogenesis as well as attenuation of oxidative stress and inflammation. Clinical data systematically confirm this beneficial effect on the endothelium, whereas the evidence concerning the effect on the microcirculation is conflicting. CONCLUSION: Preclinical and clinical studies indicate that SGLT2 inhibitors attenuate endothelial and microvascular dysfunction via a combination of mechanisms, which play a role in their beneficial cardiovascular effect.
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Dimitriadis et al. (2023) conducted a review in Heart failure and endothelial/microvascular dysfunction. SGLT2 inhibitors was evaluated. SGLT2 inhibitors attenuate endothelial and microvascular dysfunction via multiple mechanisms, contributing to their beneficial cardiovascular effects.
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