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Smooth muscle NF90 deficiency ameliorates diabetic atherosclerotic calcification in male mice via FBXW7-AGER1-AGEs axis.
- Source :
-
Nature communications [Nat Commun] 2024 Jun 11; Vol. 15 (1), pp. 4985. Date of Electronic Publication: 2024 Jun 11. - Publication Year :
- 2024
-
Abstract
- Hyperglycemia accelerates calcification of atherosclerotic plaques in diabetic patients, and the accumulation of advanced glycation end products (AGEs) is closely related to the atherosclerotic calcification. Here, we show that hyperglycemia-mediated AGEs markedly increase vascular smooth muscle cells (VSMCs) NF90/110 activation in male diabetic patients with atherosclerotic calcified samples. VSMC-specific NF90/110 knockout in male mice decreases obviously AGEs-induced atherosclerotic calcification, along with the inhibitions of VSMC phenotypic changes to osteoblast-like cells, apoptosis, and matrix vesicle release. Mechanistically, AGEs increase the activity of NF90, which then enhances ubiquitination and degradation of AGE receptor 1 (AGER1) by stabilizing the mRNA of E3 ubiquitin ligase FBXW7, thus causing the accumulation of more AGEs and atherosclerotic calcification. Collectively, our study demonstrates the effects of VSMC NF90 in mediating the metabolic imbalance of AGEs to accelerate diabetic atherosclerotic calcification. Therefore, inhibition of VSMC NF90 may be a potential therapeutic target for diabetic atherosclerotic calcification.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Male
Mice
Humans
Vascular Calcification metabolism
Vascular Calcification pathology
Vascular Calcification genetics
Mice, Inbred C57BL
Ubiquitination
Diabetes Mellitus, Experimental metabolism
Diabetes Mellitus, Experimental complications
Diabetes Mellitus, Experimental genetics
Diabetes Mellitus, Experimental pathology
Hyperglycemia metabolism
Hyperglycemia genetics
Plaque, Atherosclerotic metabolism
Plaque, Atherosclerotic pathology
Plaque, Atherosclerotic genetics
Apoptosis
Glycation End Products, Advanced metabolism
Muscle, Smooth, Vascular metabolism
Muscle, Smooth, Vascular pathology
Mice, Knockout
Atherosclerosis metabolism
Atherosclerosis genetics
Atherosclerosis pathology
F-Box-WD Repeat-Containing Protein 7 metabolism
F-Box-WD Repeat-Containing Protein 7 genetics
Myocytes, Smooth Muscle metabolism
Myocytes, Smooth Muscle pathology
Nuclear Factor 90 Proteins metabolism
Nuclear Factor 90 Proteins genetics
Receptor for Advanced Glycation End Products metabolism
Receptor for Advanced Glycation End Products genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 38862515
- Full Text :
- https://doi.org/10.1038/s41467-024-49315-9