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Secretoneurin Gene Therapy Improves Hind Limb and Cardiac Ischemia in Apo E -/- mice Without Influencing Systemic Atherosclerosis.
MedLine Citation:
PMID:  25377726     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIMS: Hypercholesterolemia is a major risk factor for cardiovascular diseases and has been shown to influence angiogenesis in the hind limb ischemia (HLI) model. The impaired up-regulation of angiogenic factors seems to be one of the underlying mechanisms for reduced vessel formation. Since we found that secretoneurin (SN) is up-regulated in hypoxic skeletal muscle cells and exerts beneficial effects in myocardial and hind limb ischemia, we hypothesized that SN-therapy might improve neovascularization in hypercholesterolemic Apo E -/- mice suffering from an impaired vascular response.
METHODS AND RESULTS: For in-vitro experiments endothelial cells (EC) were incubated with oxidized low-density lipoprotein (oxLDL) to mimic hypercholesterolemia. EC function was impaired by oxLDL but SN induced EC proliferation and in-vitro tube formation under these conditions. In the HLI-model injection of SN-plasmid resulted in a significant better outcome regarding blood flow recovery, amputation rate and vessel density. In the myocardial infarction (MI) model the SN-group showed improvement of cardiac parameters. Aortic plaque area wasn't influenced by local SN-injection. Interestingly, SN-induced recruitment of angiogenic monocytic cells was abolished under hypercholesterolemia.
CONCLUSIONS: SN-gene therapy exerts beneficial effects in cardiovascular animal models in Apo E -/- mice without influencing atherosclerosis and might qualify as a promising therapy for cardiovascular disorders.
Authors:
Markus Theurl; Wilfried Schgoer; Karin Albrecht-Schgoer; Daniela Lener; Dominik Wolf; Maria Wolf; Egon Demetz; Piotr Tymoszuk; Ivan Tancevski; Reiner Fischer-Colbrie; Wolfgang-Michael Franz; Peter Marschang; Rudolf Kirchmair
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-5
Journal Detail:
Title:  Cardiovascular research     Volume:  -     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-7     Completed Date:  -     Revised Date:  2014-11-8    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.
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