دورية أكاديمية
Progressive Development of Aberrant Smooth Muscle Cell Phenotype in Abdominal Aortic Aneurysm Disease.
| العنوان: | Progressive Development of Aberrant Smooth Muscle Cell Phenotype in Abdominal Aortic Aneurysm Disease. |
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| المؤلفون: | Riches K; Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM), University of Leeds, Leeds, UK., Clark E, Helliwell RJ, Angelini TG, Hemmings KE, Bailey MA, Bridge KI, Scott DJA, Porter KE |
| المصدر: | Journal of vascular research [J Vasc Res] 2018; Vol. 55 (1), pp. 35-46. Date of Electronic Publication: 2017 Dec 13. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: S. Karger Country of Publication: Switzerland NLM ID: 9206092 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1423-0135 (Electronic) Linking ISSN: 10181172 NLM ISO Abbreviation: J Vasc Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Basel ; New York : S. Karger, c1992- |
| مواضيع طبية MeSH: | Aortic Aneurysm, Abdominal/*pathology , Aortic Rupture/*pathology , Muscle, Smooth/*pathology , Myocytes, Smooth Muscle/*pathology, Animals ; Aorta, Abdominal/metabolism ; Aorta, Abdominal/pathology ; Aortic Aneurysm, Abdominal/complications ; Aortic Aneurysm, Abdominal/metabolism ; Aortic Rupture/etiology ; Aortic Rupture/metabolism ; Cell Differentiation ; Cell Shape ; Cells, Cultured ; Cellular Senescence ; DNA Damage ; Dilatation, Pathologic ; Disease Progression ; Histones/metabolism ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Muscle, Smooth/metabolism ; Myocytes, Smooth Muscle/metabolism ; Phenotype ; Sirtuin 1/metabolism ; Sus scrofa |
| مستخلص: | Abdominal aortic aneurysm (AAA) is a silent, progressive disease with a high mortality and an increasing prevalence with aging. Smooth muscle cell (SMC) dysfunction contributes to gradual dilatation and eventual rupture of the aorta. Here we studied phenotypic characteristics in SMC cultured from end-stage human AAA (≥5 cm) and cells cultured from a porcine carotid artery (PCA) model of early and end-stage aneurysm. Human AAA-SMC presented a secretory phenotype and expressed elevated levels of the differentiation marker miR-145 (2.2-fold, p < 0.001) and the senescence marker SIRT-1 (1.3-fold, p < 0.05), features not recapitulated in aneurysmal PCA-SMC. Human and end-stage porcine aneurysmal cells were frequently multi-nucleated (3.9-fold, p < 0.001, and 1.8-fold, p < 0.01, respectively, vs. control cells) and displayed an aberrant nuclear morphology. Human AAA-SMC exhibited higher levels of the DNA damage marker γH2AX (3.9-fold, p < 0.01, vs. control SMC). These features did not correlate with patients' chronological age and are therefore potential markers for pathological premature vascular aging. Early-stage PCA-SMC (control and aneurysmal) were indistinguishable from one another across all parameters. The principal limitation of human studies is tissue availability only at the end stage of the disease. Refinement of a porcine bioreactor model would facilitate the study of temporal modulation of SMC behaviour during aneurysm development and potentially identify therapeutic targets to limit AAA progression. (© 2017 S. Karger AG, Basel.) |
| معلومات مُعتمدة: | PG/17/7/32806 United Kingdom BHF_ British Heart Foundation |
| فهرسة مساهمة: | Keywords: Abdominal aortic aneurysm, human; Aging; DNA damage; Senescence; Smooth muscle cells |
| المشرفين على المادة: | 0 (H2AX protein, human) 0 (Histones) 0 (MIRN145 microRNA, human) 0 (MicroRNAs) EC 3.5.1.- (SIRT1 protein, human) EC 3.5.1.- (Sirtuin 1) |
| تواريخ الأحداث: | Date Created: 20171213 Date Completed: 20180618 Latest Revision: 20231115 |
| رمز التحديث: | 20231115 |
| DOI: | 10.1159/000484088 |
| PMID: | 29232676 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1423-0135 |
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| DOI: | 10.1159/000484088 |