Inhibition of a novel Dickkopf-1-LDL receptor–related proteins 5 and 6 axis prevents diabetic cardiomyopathy in mice
Authors' conclusion
These findings establish a novel DKK1-LRP5/6-GPCR pathway in inducing diabetic injuries and may resolve the long-standing conundrum as to why elevated blood DKK1 has deleterious effects.
Study context
- Population
- Humans and diabetic mice
Main finding
As reported in the abstract
- BP up-regulation positively correlated with serum DKK1 elevations in humans
- LRP5/6 physically and functionally interacted with AT1R
- Loss of membrane LRP5/6 (recombinant DKK1 injection or conditional LRP5/6 deletion) caused AT1R activation and hypertension, plus β-arrestin1 activation and cardiac impairment
- Anti-DKK1 neutralizing antibody, unlike common anti-hypertensive agents, prevented diabetic cardiac impairment in mice
Original publication
Inhibition of a novel Dickkopf-1-LDL receptor–related proteins 5 and 6 axis prevents diabetic cardiomyopathy in mice. Eur Heart J. Published 28 December 2023. doi:10.
Summarised from the published abstract; every number is checked against it