期刊
LANCET DIABETES & ENDOCRINOLOGY
卷 2, 期 5, 页码 427-436出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/S2213-8587(14)70059-2
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资金
- Amgen
- Astellas
- AbbVie
- Shire
- Sanofi
- Pfizer
- Dutch Kidney Foundation
- Baxter
- FMC
- Sanofi/Genzyme
- Chugai
- Abbott
- Vifor
- Amgen AbbVie
- Fresenius
- AstraZeneca
- Synlab
- Genzyme
Recent reports of several bone-derived substances, some of which have hormonal properties, have shed new light on the bone-cardiovascular axis. Deranged concentrations of humoral factors are not only epidemiologically connected to cardiovascular morbidity and mortality, but can also be causally implicated, especially in chronic kidney disease. FGF23 rises exponentially with advancing chronic kidney disease, seems to reach maladaptive concentrations, and then induces left ventricular hypertrophy, and is possibly implicated in the process of vessel calcification. Sclerostin and DKK1, both secreted mainly by osteocytes, are important Wnt inhibitors and as such can interfere with systems for biological signalling that operate in the vessel wall. Osteocalcin, produced by osteoblasts or released from mineralised bone, interferes with insulin concentrations and sensitivity, and its metabolism is disturbed in kidney disease. These bone-derived humoral factors might place the bone at the centre of cardiovascular disease associated with chronic kidney disease. Most importantly, factors that dictate the regulation of these substances in bone and subsequent secretion into the circulation have not been researched, and could provide entirely new avenues for therapeutic intervention.
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