David Magne (France)
University Claude Bernard Lyon 1 CNRS UMR 5246 ICBMSAuthor Of 2 Presentations
Live Q&A (ID 1550)
O006 - Tissue-nonspecific alkaline phosphatase inhibition reduces atherosclerotic plaque development (ID 1424)
Abstract
Background and Aims
The calcium score predicts cardiovascular mortality but the impact of calcification on plaque stability remains controversial. Tissue-nonspecific alkaline phosphatase (TNAP), the main enzyme involved in bone mineralization, is expressed in calcified mouse plaques, and is also elevated in the blood of individuals with metabolic syndrome, in whom it is associated with cardiovascular mortality. Therefore, we aimed to determine the involvement of TNAP in plaque calcification and progression.
Methods
TNAP activity was studied in aortic plaques, liver and blood of apoE-deficient mice fed a high fat diet from 10 weeks of age and sacrificed every two weeks from 17 to 31 weeks. Plaque calcification was imaged longitudinally with 18F-NaF PET and µCT and histologically with the calcium tracer osteosense. TNAP expression was also investigated in calcified and non-calcified human carotid plaques. TNAP was inhibited in mice using the inhibitor SBI-425 (30 mg/kg/day) from 10 weeks of age.
Results
Plaque calcification developed as cartilage metaplasia in association with TNAP activity in apoE-deficient mice. In human carotid plaques, calcification was also localized to TNAP-positive areas. In mice, short-term SBI-425 treatment prevented early plaque calcification, reduced inflammation, plaque growth and lipid accumulation, without exerting adverse effects on bone architecture. More unexpectedly, TNAP inhibition reduced serum cholesterol and triglycerides, suggesting that TNAP may slow down plaque development through direct and indirect effects.
Conclusions
In conclusion, this study demonstrates that TNAP activity strongly impacts plaque development, by effects probably not restricted to plaque calcification.
Presenter of 2 Presentations
Live Q&A (ID 1550)
O006 - Tissue-nonspecific alkaline phosphatase inhibition reduces atherosclerotic plaque development (ID 1424)
Abstract
Background and Aims
The calcium score predicts cardiovascular mortality but the impact of calcification on plaque stability remains controversial. Tissue-nonspecific alkaline phosphatase (TNAP), the main enzyme involved in bone mineralization, is expressed in calcified mouse plaques, and is also elevated in the blood of individuals with metabolic syndrome, in whom it is associated with cardiovascular mortality. Therefore, we aimed to determine the involvement of TNAP in plaque calcification and progression.
Methods
TNAP activity was studied in aortic plaques, liver and blood of apoE-deficient mice fed a high fat diet from 10 weeks of age and sacrificed every two weeks from 17 to 31 weeks. Plaque calcification was imaged longitudinally with 18F-NaF PET and µCT and histologically with the calcium tracer osteosense. TNAP expression was also investigated in calcified and non-calcified human carotid plaques. TNAP was inhibited in mice using the inhibitor SBI-425 (30 mg/kg/day) from 10 weeks of age.
Results
Plaque calcification developed as cartilage metaplasia in association with TNAP activity in apoE-deficient mice. In human carotid plaques, calcification was also localized to TNAP-positive areas. In mice, short-term SBI-425 treatment prevented early plaque calcification, reduced inflammation, plaque growth and lipid accumulation, without exerting adverse effects on bone architecture. More unexpectedly, TNAP inhibition reduced serum cholesterol and triglycerides, suggesting that TNAP may slow down plaque development through direct and indirect effects.
Conclusions
In conclusion, this study demonstrates that TNAP activity strongly impacts plaque development, by effects probably not restricted to plaque calcification.