Journal
RHEUMATOLOGY
Volume 61, Issue 7, Pages 3071-3081Publisher
OXFORD UNIV PRESS
DOI: 10.1093/rheumatology/keab788
Keywords
FABP3; fibrosis; fatty acid oxidation; Takayasu's arteritis; aorta adventitia fibroblasts
Categories
Funding
- National Nature Science Foundation of China [81771730]
- National Youth Natural Science Foundation of China [81901639]
Ask authors/readers for more resources
This study identified the role of FABP3 in vascular fibrosis in TAK and explored the underlying molecular mechanism. The expression of FABP3 was increased in the thickened adventitia of TAK patients and positively correlated with the serum expression of ECMs. FABP3 knockdown inhibited AAF proliferation and ECM production, while FABP3 overexpression enhanced these processes. Further analysis revealed that FABP3 upregulation promoted FAO and ATP production in AAFs. FABP3 and CACT were co-localized in the adventitia and bound to each other in AAFs. Etomoxir reversed the enhanced FAO, ATP production, AAF proliferation, and ECM production mediated by FABP3 upregulation. Treatment with curcumin reduced the level of serum FABP3 and inhibited vascular fibrosis by reducing FABP3-enhanced FAO in AAFs.
Objective To identify the role of fatty acid binding protein 3 (FABP3) in vascular fibrosis in Takayasu's arteritis (TAK) and to explore the underlying molecular mechanism. Methods The expression of FABP3 and extracellular matrix proteins (ECMs) were detected in aorta tissues from TAK patients (n = 12) and healthy controls (n = 8) by immunohistochemistry. The concentration of serum proteins was determined by ELISA. CCK8 and Ki67 staining were used to measure aorta adventitial fibroblast (AAF) proliferation. Widely targeted lipidomic profiling was used to screen for associated metabolic pathways. Changes in ECMs and fatty acid oxidation (FAO)-related enzymes were determined by RT-qPCR and Western blot. The interactions between FABP3 and these enzymes were explored with a co-immunoprecipitation (Co-IP) assay. Results The expression of FABP3 was increased in the thickened adventitia of TAK patients and was positively correlated with the serum expression of ECMs. FABP3 knockdown inhibited AAF proliferation and ECM production, whereas FABP3 overexpression enhanced these processes. Further analysis revealed that FABP3 upregulation promoted carnitine palmitoyltransferase 1A and carnitine/acylcarnitine carrier protein (CACT) expression, two key enzymes in FAO, as well as adenosine triphosphate (ATP) levels. FABP3 and CACT were co-localized in the adventitia and bound to each other in AAFs. Etomoxir reversed the enhanced FAO, ATP production, AAF proliferation and ECM production mediated by FABP3 upregulation. Treatment with 60 g/day curcumin granules for 3 months reduced the level of serum FABP3. Curcumin also inhibited vascular fibrosis by reducing FABP3-enhanced FAO in AAFs. Conclusion Elevated FABP3 expression accelerated vascular fibrosis in TAK, which was likely mediated by promoting FAO in AAFs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available