Empagliflozin reduces neointimal formation and vascular smooth muscle cell proliferation via the suppression of PDGF-related signaling
Abstract
Abstract Objective Emerging evidence has documented the beneficial effects of sodium glucose cotransporter 2 (SGLT2) inhibitors on reducing cardiovascular events. Beyond glucose regulation, the mechanisms behind their cardioprotective effects still remained unresolved. This study aims to investigate whether these benefits are mediated by their effects on vascular smooth muscle cell (VSMC) functions. Approach and Results Treatment of non-diabetic rats with empagliflozin (a SGLT2 inhibitor) attenuated balloon injury-induced neointimal formation in carotid arteries. In vitro , treatment of rat VSMCs with empagliflozin reduced platelet-derived growth factor (PDGF)-BB-induced proliferation and migration. Moreover, empagliflozin-treated VSMCs did not undergo apoptosis and cytosis. Notably, treating VSMCs with empagliflozinsuppressed the activation of PDGF-related signaling, such as that related to the phosphorylation of PDGF receptor b (PDGF-Rb), Akt, and STAT3. Furthermore, overactivation of PDGF-related signaling attenuated the inhibitory effects of empagliflozin on VSMC proliferation and migration. The relevant in vitro findings were corroborated in the neointima of empagliflozin-treated rats. The fact that minimal SGLT2 was discovered in rat VSMCs and SGLT2 silencing did not alter the effect of empagliflozin supported the SGLT2-independent effect of empagliflozin on VSMC functions. Conclusions This study highlights the crucial role of PDGF-related signaling in mediating the…
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Evidence Hub reads this as a preprint, done in animal, not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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