Abstract: SA-PO977
Indoxyl Sulfate Aggravates Vascular Calcification via Suppress the Matrix Gla Protein by the the ROS/NF-κB Signaling Pathway
Session Information
- Hypertension and CVD: Mechanisms - II
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- He, Xin, Xi'an Jiaotong University, Xi'an, China
- Jiang, Hongli, First Affiliated Hospital of Medicine School, Xi?an Jiaotong University, Xi?an, China
Background
Vascular calcification (VC) is the major complication and contributes to the cardiovascular mortality in chronic kidney diseases (CKD). Indoxyl sulfate (IS) has been recognized as the major uremic toxin involved in the vascular calcification in CKD due to its high oxidative stress, but the underlying mechanisms remain largely unknown. Matrix Gla protein (MGP) plays roles in vascular calcification as an important inhibitor of calcification. Here, we investigated whether MGP is involved in IS-induced vascular calcification.
Methods
In vitro, radial arteries from CKD patients were used for histological examination. In vitro, HASMCs were cultured with IS to induce vascular calcification, which was detected by Alizarin red S staining. Gene expression and protein levels of MGP and osteogenic differentiation markers were determined by qRT-PCR and western blotting, respectively. ROS were detected using probes with a fluorescence detector. The phosphorylation of Ikkβ, NF-κB and IκB degradation were detected by western blotting, and the role of ROS/NF-κB was further confirmed by using the inhibitor of DPI and PDTC.
Results
We observed the average level of MGP expression was decreased in the calcified vessels in CKD patients.
Simultaneously, IS also decreased MGP expression accompanied by the calcification of HASMCs. osteogenic differentiation was confirmed by the increased expression of BMP2 and Cbfa1 and decreased expression of the α-SMA, which was accompanied by the increased level of ROS. The phosphorylation of Ikkβ, NF-κB and IκB degradation increased by IS but reversed by an ROS inhibitor of DPI. In contrast, suppression of MGP and calcification of HASMCs calcification were attenuated by pretreatment with PDTC, an NF-κB inhibitor.
Conclusion
These observations provide evidence that inhibition of MGP expression may contribute to the pathogenesis of IS-induced vascular calcification in CKD.
Funding
- Government Support - Non-U.S.