Document Detail


Inhibition of caspase-3 differentially affects vascular smooth muscle cell apoptosis in the concave versus convex aortic sites in ascending aneurysms with a bicuspid aortic valve.
MedLine Citation:
PMID:  20427168     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Apoptosis of vascular smooth muscle cells (VSMCs) is involved in bicuspid aortic valve (BAV) ascending aorta aneurysms characteristically affecting the convex site. Caspase-3 is a pivotal effector of the apoptosis machinery. The aim of this study was to investigate the impact of an inhibited caspase-3 pathway on apoptosis in convex and concave sites VSMCs of ascending aortic tissue in vitro. Specimens from the convex and concave sites of ascending aortic aneurysm were collected from nine patients with BAV (mean age 58.7+/-14.8). Cultured VSMCs were characterized morphologically and immunohistochemically. Apoptosis activity was measured in VSMCs using Annexin V-APC with propidium iodide nuclear staining in flow cytometry. To investigate apoptotic modulation, caspase-3 was inhibited by N-acetyl-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO). Apoptosis was initiated by calcium chloride. Inhibition of caspase-3 with Ac-DEVD-CHO protected VSMCs against calcium chloride apoptosis significantly more in the concave site than in the convex site (25.8+/-9.8 versus 38.5+/-8.0% apoptotic cells, p=0.01). Morphological scanning using light microscopy revealed typical VSMCs. We provide evidence that VSMCs show a different behavior with respect to apoptosis in the concave versus the convex sites in BAV ascending aortic aneurysm. Inhibition of caspase-3 resulted in a significantly increased protection of VSMCs against apoptosis in the concave site compared with the convex site in ascending aortic aneurysm in BAV. These findings may have some implications on understanding aneurysmal formation and its potential modulation.
Authors:
S A Mohamed; M Misfeld; T Hanke; E I Charitos; J Bullerdiek; G Belge; W Kuehnel; H H Sievers
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Publication Detail:
Type:  Journal Article     Date:  2010-04-11
Journal Detail:
Title:  Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft     Volume:  192     ISSN:  1618-0402     ISO Abbreviation:  Ann. Anat.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-14     Completed Date:  2010-09-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100963897     Medline TA:  Ann Anat     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  145-50     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier GmbH. All rights reserved.
Affiliation:
University Clinic of Schleswig-Holstein, Department of Cardiac Surgery, D-23538 Luebeck, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aneurysm / pathology*
Aorta / pathology*
Apoptosis
Caspase 3 / antagonists & inhibitors*
Cell Culture Techniques
Female
Flow Cytometry
Heart Valves / pathology*
Humans
Hypertension / pathology
Male
Middle Aged
Muscle, Smooth, Vascular / pathology*
Protein Array Analysis
Pulmonary Disease, Chronic Obstructive / pathology
Chemical
Reg. No./Substance:
EC 3.4.22.-/Caspase 3

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