The Inhibitory Effects of Canagliflozin on Nicotine-induced Arterial Stiffness and Its Mechanism

doi:10.3870/j.issn.1672-0741.25.12.035

Abstract

Abstract: Objective To investigate the effects of canagliflozin on nicotine-induced arterial stiffness,and its possible mechanisms of action.Methods An animal model of nicotine-induced arterial stiffness was established by subcutaneously implanting osmotic microinfusion pumps into C57BL/6 mice to deliver a continuous infusion of nicotine;the model animals were then treated with canagliflozin to explore the effect of canagliflozin on arterial stiffness in these animals.In the in vivo experiments,ultrasound technology was employed to measure the aortic pulse wave velocity(PWV)in mice;aortic histopathology and vascular remodeling were examined using hematoxylin-eosin(HE)staining,Masson's trichrome staining,and Verhoeff's van Gieson(EVG)staining.Additionally,Western blot and immunofluorescence techniques were employed to detect the expression levels of matrix metalloproteinase-2(MMP-2),MMP-9,collagen Ⅰ,and fibronectin.Nicotine-treated murine aortic smooth muscle cells(Movas)were treated with canagliflozin in vitro,and Western blot analysis was used to detect changes in the expression of key proteins in the transforming growth factor-β1(TGF-β1)signaling pathway.Results Compared with mice in the control group,canagliflozin significantly suppressed the nicotine-induced increase in PWV in mice,also significantly reduced collagen fibre deposition and elastic fibre degradation.Furthermore,canagliflozin significantly downregulated the nicotine-induced expression of Collagen Ⅰ,fibronectin,MMP2 and MMP9 at the protein level,whilst also significantly inhibiting the nicotine-mediated increase in CollagenⅠ and MMP2 mRNA levels.In vitro experiments revealed that nicotine significantly up-regulated the expression of TGF-β1 and Smad2/Smad3 in mouse aortic smooth muscle cells,whereas canagliflozin significantly reversed the nicotine-induced up-regulation of these molecules.Conclusion Canagliflozin markedly suppressed nicotine-induced arterial stiffness in mice,potentially through its significant inhibition of nicotine-induced collagen fibre deposition and elastic fiber degradation.This effect may involve canagliflozin-mediated suppression of TGF-β1/Smad signaling pathway in mouse aortic smooth muscle cells.

Key words: canagliflozin, nicotine, arterial stiffness, TGF-β1

CLC Number:

R543.5

Dong Pan, He Yang, Li Yixiao, et al. The Inhibitory Effects of Canagliflozin on Nicotine-induced Arterial Stiffness and Its Mechanism[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(4): 475-482.

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