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.

PubMed

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.

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