Asset Details
Do you wish to reserve the book?
Evogliptin prevents ceramide-induced pyroptosis during calcification via modulation of NLRP3/GSDM-D mediated pathway in Vascular Smooth Muscle Cells
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Evogliptin prevents ceramide-induced pyroptosis during calcification via modulation of NLRP3/GSDM-D mediated pathway in Vascular Smooth Muscle Cells
Do you wish to request the book?
Evogliptin prevents ceramide-induced pyroptosis during calcification via modulation of NLRP3/GSDM-D mediated pathway in Vascular Smooth Muscle Cells
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Evogliptin prevents ceramide-induced pyroptosis during calcification via modulation of NLRP3/GSDM-D mediated pathway in Vascular Smooth Muscle Cells
2025
Overview
Evogliptin, an anti-diabetic drug had positive impact on various cardiovascular events including inflammation and vascular calcification (VC), an active process driven by vascular smooth muscle cell (VSMC) phenotypic transition. Sphingolipids such as ceramide (CER) mediates inflammation and VC in the vascular tissue. We investigated whether evogliptin ameliorate phenotypic transition and pyroptosis in VSMCs as underlying cause of VC. In cultured VSMCs, isolated from the aorta of (C57/BL6) mouse, we observed more severe calcification with prior treatment of CER in Pi-treated VSMCs as detected by Alizarin Red Staining. Prior CER- stimulation led to a marked upregulation of osteogenic markers such as RUNX2, OPN, BMP2 and decreased contractile markers SM22-α and α- SMA in Pi-treated VSMCs as compared to control cells. In addition, increased expression of pyroptotic markers such as NLRP3, GSDM-D, IL-1β, IL-18, and LDH release was observed with prior treatment of CER in Pi-treated VSMCs as compared to control cells. Furthermore, MCC950 (NLRP3 inhibitor), disulfiram (GSDM-D inhibitor) and evogliptin significantly downregulated osteogenic and pyroptotic markers including LDH release in both Pi-induced only and CER + Pi-treated VSMCs. Moreover, GW4869 (SMase inhibitor) and evogliptin significantly reduced SMase activity in sphingomyelin (SM)-induced VSMCs as compared to both Pi and SM only-treated groups. Also, the cleavage efficiency of GSDM-D was high in Pi and CER + Pi groups which was reduced with prior treatment of evogliptin. Hence, our data demonstrate that evogliptin alleviates VC by blocking phenotypic transition and associated pyroptosis via modulation of NLRP3/GSDM-D mediated pathway in CER-induced VSMCs.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Animals
/ Aorta
/ Ceramide
/ Complications and side effects
/ Diabetes
/ Male
/ Mice
/ Muscle, Smooth, Vascular - cytology
/ Muscle, Smooth, Vascular - drug effects
/ Muscle, Smooth, Vascular - metabolism
/ Muscle, Smooth, Vascular - pathology
/ Myocytes, Smooth Muscle - drug effects
/ Myocytes, Smooth Muscle - metabolism
/ Myocytes, Smooth Muscle - pathology
/ NLR Family, Pyrin Domain-Containing 3 Protein - metabolism
/ Proteins
/ Scanning electron microscopy
/ Signal Transduction - drug effects
/ Testing
/ Vascular Calcification - drug therapy
/ Vascular Calcification - metabolism
