Skip to main content
main-content

20.06.2020 | Routine Article | Ausgabe 5/2020

Cardiovascular Drugs and Therapy 5/2020

Diallyl Trisulfide Suppresses Angiotensin II–Induced Vascular Remodeling Via Inhibition of Mitochondrial Fission

Zeitschrift:
Cardiovascular Drugs and Therapy > Ausgabe 5/2020
Autoren:
Zhao-Yang Lu, Jia Qi, Bin Yang, Hui-Li Cao, Rui-Ying Wang, Xuan Wang, Rui-Fang Chi, Chun-Ling Guo, Zhi-Ming Yang, Hui-Min Liu, Bao Li
Wichtige Hinweise
Zhao-Yang Lu, Jia Qi and Bin Yang contributed equally to this work.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Abstract

Objective

We have shown previously that diallyl trisulfide (DATS) ameliorates mitochondrial fission and oxidative stress in a hyperglycemia-induced endothelial apoptosis and diabetic mouse model. The aim of this study was to investigate whether DATS mitigates Ang II-induced vascular smooth muscle cell (VSMC) phenotypic switching and vascular remodeling, and if so, to determine the underlying molecular events.

Methods

Male C57BL/6 mice were used to establish a vascular remodeling model by continuous 2-week Ang II infusion using a subcutaneous osmotic pump. Animals were intraperitoneally injected with DATS or vehicle. Physiological parameters, vascular morphology, and molecular markers were assessed. For in vitro studies, VSMCs were pretreated with or without DATS for 1 h, then were stimulated with Ang II, and mitochondrial morphology and phenotypic switching of VSMCs were also measured.

Results

In primary mouse VSMCs, we found that Drp1-dependent mitochondrial fission regulated mitochondrial reactive oxygen species (mtROS) generation, which eventually promoted Ang II-induced VSMC proliferation, migration, and phenotypic switching. Moreover, Ang II was found to up-regulate the Rho-associated coiled coil-containing protein kinase 1 (ROCK1), which regulated mitochondrial fission and VSMC phenotypic switching by phosphorylating Drp1. However, the biological effect of Ang II was abrogated by DATS. Consistent with the effects in VSMCs, we found that DATS markedly alleviated mitochondrial fission, VSMC differentiation, and vessel wall thickening in an animal model of Ang II-induced vascular remodeling, which was regulated by the ROCK1/Drp1 signal.

Conclusions

Our findings showed that DATS mitigated Ang II-induced vascular remodeling by suppressing Drp1-mediated mitochondrial fission in an ROCK1-dependent manner.

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

★ PREMIUM-INHALT
e.Med Interdisziplinär

Für Ihren Erfolg in Klinik und Praxis - Die beste Hilfe in Ihrem Arbeitsalltag als Mediziner

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de.

Weitere Produktempfehlungen anzeigen
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 5/2020

Cardiovascular Drugs and Therapy 5/2020 Zur Ausgabe
  1. Sie können e.Med Innere Medizin 14 Tage kostenlos testen (keine Print-Zeitschrift enthalten). Der Test läuft automatisch und formlos aus. Es kann nur einmal getestet werden.

Neu im Fachgebiet Kardiologie

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Kardiologie und bleiben Sie gut informiert – ganz bequem per eMail.

Bildnachweise