Vasculoprotective Effects of Sodium-Glucose Co-Transporter Inhibitors in Non-Diabetic Experimental Settings: A Narrative Review

TL;DR

This review explores how SGLT inhibitors, typically used for diabetes, protect blood vessels and reduce heart disease risks in non-diabetic models.

Contribution

The paper provides a narrative review on the direct vasculoprotective effects of SGLT2 and dual SGLT1/2 inhibitors in non-diabetic experimental settings.

Findings

SGLT inhibitors improve vascular health by reducing inflammation and oxidative stress.

They alleviate endothelial dysfunction and arterial stiffness, leading to lower blood pressure.

Both chronic and acute cardiovascular benefits are supported by experimental and cellular studies.

Abstract

Sodium-glucose co-transporter (SGLT) inhibitors are a novel class of glucose-lowering drugs with beneficial pleiotropic effects that have been widely investigated in the past decade in several experimental models and patients in the absence of diabetes. There are two types of transporters: the SGLT1 isoform that is distributed across a broad range of tissues, including the cardiovascular system, and the SGLT2 isoform, which is mostly expressed in renal proximal tubular cells. It is known that inflammation and oxidative stress are key contributors to vascular damage and the progression of atherosclerosis. SGLT inhibitors have demonstrated multiple benefits that contribute to improved vascular health, including alleviation of endothelial function, anti-inflammatory and antioxidative effects, and mitigation of arterial stiffness, all contributing to blood pressure decrease. An increasing body of research has tackled the molecular and cellular mechanisms of their chronic and, more recently, acute cardiovascular beneficial effects. This narrative review specifically delves into the direct vasculoprotective effects of SGLT2 and dual SGLT1/2 inhibitors, summarizing their off-target mechanisms described in various experimental settings (animal models, animal and human cell lines/samples).

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