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Updated: Feb 24, 2026

A Semi-Automated and Reproducible Biological-Based Method to Quantify Calcium Deposition In Vitro
Published on: June 2, 2022
Vericiguat improves CKD-related vascular calcification through the NO/cGMP/PKG pathway
Chengsi Li1, Jing Li1, Chengyingjie Yang1
1Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665, Kongjiang Road, Shanghai 200000, China.
Insights
Vericiguat, a soluble guanylyl cyclase sensitizer, effectively treats vascular calcification in chronic kidney disease (CKD) by activating the NO/cGMP/PKG pathway. This finding offers new therapeutic avenues for CKD patients at high cardiovascular risk.
Area of Science:
- Nephrology
- Cardiovascular Research
- Pharmacology
Background:
- Chronic kidney disease (CKD) leads to progressive kidney function loss.
- Vascular calcification is a common CKD complication and predictor of cardiovascular events.
- Soluble guanylyl cyclase (sGC) sensitizers represent a potential therapeutic strategy.
Purpose of the Study:
- To investigate the mechanism of vericiguat (VER) in attenuating CKD-associated vascular calcification.
- To verify if VER alleviates decreased sGC activity due to calcium and phosphorus metabolism.
- To explore the role of the NO/cGMP/PKG pathway in VER's therapeutic effects.
Main Methods:
- In vitro and in vivo experimental models of CKD-associated vascular calcification.
- Assessment of calcium levels, osteogenic markers, eNOS, and PKG expression.
- Measurement of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels.
- Inhibition studies using L-NAME to antagonize VER effects.
Main Results:
- Increased calcium levels and upregulation of osteogenic markers were observed in CKD rat aortas and VSMCs.
- Vericiguat significantly improved calcification by activating the NO/cGMP/PKG pathway.
- L-NAME reversed the beneficial effects of vericiguat, confirming pathway involvement.
Conclusions:
- Vericiguat effectively attenuates vascular calcification in CKD models.
- The therapeutic effect of vericiguat is mediated through the NO/cGMP/PKG pathway.
- Vericiguat shows promise for managing vascular complications in CKD patients.
Abstract:
Chronic kidney disease (CKD) is a condition characterized by progressive loss of kidney function. Vascular calcification is not only a common late-stage complication of CKD but also serves as an independent predictor of cardiovascular events and mortality in CKD patients. This study investigates the mechanism by which vericiguat (VER), a soluble guanylyl cyclase (sGC) sensitizer, attenuates CKD-associated vascular calcification. The hypothesis that vericiguat alleviates the decrease of sGC activity mediated by calcium and phosphorus metabolism was verified in both in vitro and in vivo experimental models. The calcium levels were increased in the aorta of CKD rats and VSMCs in vitro, and the expression of osteogenic differentiation-related markers, eNOS and PKG was upregulated. Nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels were downregulated, while VER significantly improved calcification by activating the NO/cGMP/PKG pathway. Meanwhile, L-NAME antagonized the positive effects of VER in either CKD rats or calcified VSMCs.
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