RÉSUMÉ
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.
Sujet(s)
Athérosclérose , Protéine-7 contenant une boite F et des répétitions WD , Produits terminaux de glycation avancée , Souris knockout , Muscles lisses vasculaires , Myocytes du muscle lisse , Facteurs nucléaires-90 , Récepteur spécifique des produits finaux de glycosylation avancée , Animaux , Mâle , Souris , Produits terminaux de glycation avancée/métabolisme , Muscles lisses vasculaires/métabolisme , Muscles lisses vasculaires/anatomopathologie , Athérosclérose/métabolisme , Athérosclérose/génétique , Athérosclérose/anatomopathologie , Humains , Protéine-7 contenant une boite F et des répétitions WD/métabolisme , Protéine-7 contenant une boite F et des répétitions WD/génétique , Myocytes du muscle lisse/métabolisme , Myocytes du muscle lisse/anatomopathologie , Facteurs nucléaires-90/métabolisme , Facteurs nucléaires-90/génétique , Récepteur spécifique des produits finaux de glycosylation avancée/métabolisme , Récepteur spécifique des produits finaux de glycosylation avancée/génétique , Calcification vasculaire/métabolisme , Calcification vasculaire/anatomopathologie , Calcification vasculaire/génétique , Souris de lignée C57BL , Ubiquitination , Diabète expérimental/métabolisme , Diabète expérimental/complications , Diabète expérimental/génétique , Diabète expérimental/anatomopathologie , Hyperglycémie/métabolisme , Hyperglycémie/génétique , Plaque d'athérosclérose/métabolisme , Plaque d'athérosclérose/anatomopathologie , Plaque d'athérosclérose/génétique , ApoptoseRÉSUMÉ
The "hot cross bun" sign (HCBs) is a cruciform hyperintensity on T2-weighted imaging within the pons initially found in patients diagnosed as multiple system atrophy. However, recent findings have broadened the disease spectrum presented with HCBs. Here is a case report at an academic medical center. Cerebral magnetic resonance imaging (MRI), electroneuromyography, serum, and CSF analysis were performed. Literature is comprehensively reviewed. We investigated a woman presented with blurred speech and cerebellar ataxia. Her MRI showed the vertical line of HCBs 2 weeks after disease onset and gradually enhanced, presenting as an intact HCBs in a year. Glutamic acid decarboxylase 65-kDa isoform (GAD65) antibody IgG was detected in serum and CSF. The patient was diagnosed as GAD65 associated cerebellar ataxia and treated with corticosteroid and rituximab. We found 6 previously reported autoimmune cerebellar ataxia patients with HCBs. Anti-KLHL-11, anti-Homer-3, anti-Ri, and anti-Amphiphysin were associated. All patients had cerebellar ataxia with other neurological symptoms. Five patients were diagnosed with tumor. First-line immunotherapy including corticosteroid, intravenous immunoglobulin, and plasma exchange for most patients was unsatisfied. This case highlights the importance of considering GAD65 IgG evaluation in patients with progressive cerebellar syndrome and HCBs. Early diagnosis and therapy are challenging but imperative. Further studies are required in regard to therapeutic management.