Cardioprotective function of sclerostin by reducing calcium deposition, proliferation, and apoptosis in human vascular smooth muscle cells
Authors' conclusion
Sclerostin could play a protective role in the development of atherosclerosis in T2D patients by reducing calcium deposits, decreasing proliferation and inflammation, and promoting cell survival in VSMCs under calcifying conditions. Therefore, considering the bone-vascular axis, treatment with anti-sclerostin for bone disease should be used with caution.
Study context
- Population
- T2D patients with/without cardiovascular disease (CVD) and controls; artery of lower limb from T2D patients and controls; Vascular smooth muscle cells (VSMCs) under calcifying conditionsT2D patients 7 · controls 3
- Participants
- 48 / 91 / 121
- Exposure
- T2D with CVD vs T2D without CVD vs controls; sclerostin overexpression vs mock in VSMCs
- T2D with CVDn = 48
- T2D without CVDn = 91
- Controlsn = 121reference
- Outcome
- Serum and vascular tissue sclerostin levels; role of sclerostin in VSMCs under calcified environments
Methodological detailsin vitro experiments in VSMCs
- In vitro experiments in VSMCs
Main finding
As reported in the abstract
Serum sclerostin
- Higher circulating sclerostin independently associated with CVD in T2D patients
- T2D with CVD vs T2D without CVD and controls: P < 0.001
Observational data: associations, not effects.
Further findings
| Outcome | P value |
|---|---|
| Arterial sclerostin expressionCalcified arteries of T2D patients vs Non-calcified arteries of controls · increased in calcified arteries of T2D patients | P = 0.003 |
Sclerostin overexpression vs mock in VSMCs under calcified conditions
- Reduced intracellular calcium
- P = 0.001
- Reduced calcium deposits
- P < 0.001
- Reduced cell proliferation
- P < 0.001
- Promoted cell survival
- P = 0.015
- Up-regulation of ALPL
- P = 0.009
- Up-regulation of RUNX2
- P = 0.001
- Up-regulation of COX2
- P = 0.003
- Down-regulation of IL1β
- P = 0.005
- Down-regulation of IL6
- P = 0.001
- Down-regulation of IL8
- P = 0.003
Original publication
Cardioprotective function of sclerostin by reducing calcium deposition, proliferation, and apoptosis in human vascular smooth muscle cells. Cardiovasc Diabetol. Published 2 November 2023. doi:10. 1186/ s12933-023-02043-8
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