Studies on sporadic non-syndromic thoracic aortic aneurysms: 1. Deregulation of Jagged/Notch 1 homeostasis and selection of synthetic/secretor phenotype smooth muscle cells
| Autor: | Ubaldo Armato, Alessandra Pasquali, Cristina Patuzzo, Francesco Onorati, Pier F Pignatti, Ilaria Pierpaola Dal Prà, Maddalena Marconi, Anna Maria Chiarini, Olga Irtyega, Elisabetta Trabetti, Giuseppe Faggian, Anna Malashicheva |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Pathology medicine.medical_specialty Epidemiology Blotting Western Down-Regulation Apoptosis Vimentin 030204 cardiovascular system & hematology Polymerase Chain Reaction Muscle Smooth Vascular 03 medical and health sciences Aortic aneurysm thoracic aorta 0302 clinical medicine medicine.artery Homeostasis Humans Medicine Thoracic aorta remodelling Receptor Notch1 Notch 1 smooth muscle cell Actin Tissue homeostasis Cell Proliferation Retrospective Studies Aorta Aortic Aneurysm Thoracic Glial fibrillary acidic protein biology business.industry cell signalling medicine.disease Phenotype 030104 developmental biology Gene Expression Regulation gene expression biology.protein RNA Female Cardiology and Cardiovascular Medicine business aortic aneurysm Jagged-1 Protein Signal Transduction |
| Zdroj: | European Journal of Preventive Cardiology. 25:42-50 |
| ISSN: | 2047-4881 2047-4873 |
| DOI: | 10.1177/2047487318759119 |
| Popis: | Background Sporadic non-syndromic thoracic aortic aneurysms (SNSTAAs) are less well understood than familial non-syndromic or syndromic ones. The study aimed at defining the peculiar morphologic and molecular changes occurring in the media layer of SNSTAAs. Design This study was based on a single centre design. Methods Media layer samples taken from seven carefully selected SNSTAAs and seven reference patients (controls) were investigated via quantitative polymerase chain reaction, proteomics-bioinformatics, immunoblotting, quantitative histology, and immunohistochemistry/immunofluorescence. Results In SNSTAAs media, aortic smooth muscle cells numbers were halved due to an apoptotic process coupled with a negligible cell proliferation. Cystathionine γ-lyase was diffusely up-regulated. Surviving aortic smooth muscle cells exhibited diverging phenotypes: in inner- and outer-media contractile cells prevailed, having higher contents of smooth-muscle-α-actin holoprotein (45-kDa) and of caspase-3-cleaved smooth-muscle-α-actin 25-kDa fragments; in mid-media, aortic smooth muscle cells exhibited a synthetic/secretor phenotype, down-regulating vimentin, but up-regulating glial fibrillary acidic protein, trans-Golgi network 46 protein, Jagged1 (172-kDa) holoprotein, and Jagged1’s receptor Notch1. Extracellular soluble Jagged1 (42-kDa) fragments accumulated. Conclusions In SNSTAAs, there is a relentless aortic smooth muscle cells attrition caused by the up-regulated cystathionine γ-lyase. In mid-media, synthetic/secretor aortic smooth muscle cells intensify Jagged1/NOTCH1 signalling in the attempt to counterbalance the weakened aortic wall, due to aortic smooth muscle cells net loss and mechanical stress. Synthetic/secretor aortic smooth muscle cells are apoptosis-prone, and the accruing thrombin-cleaved Jagged1 fragments counteract the otherwise useful effects of Jagged1/NOTCH1 signalling, thus hampering tissue homeostasis/remodelling, and aortic smooth muscle cells adhesion, differentiation, and migration. |
| Databáze: | OpenAIRE |
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