Academic Journal
P6292Role of CXCL12gamma isoform and its interactions with heparan-sulfates in post-ischemic cardiac remodeling
| العنوان: | P6292Role of CXCL12gamma isoform and its interactions with heparan-sulfates in post-ischemic cardiac remodeling |
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| المؤلفون: | Duval, V, Zlatanova, I, Sun, Y, Alayrac, P, Gomez, I, Lemitre, M, Vilar, J, Silvestre, J S, Levoye, A |
| المصدر: | European Heart Journal ; volume 40, issue Supplement_1 ; ISSN 0195-668X 1522-9645 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2019 |
| الوصف: | Introduction Myocardial infarction (MI) is a severe ischemic disease precipitating long-term adverse remodeling and heart failure. The chemokine CXCL12/SDF-1 is essential for cardiovascular system development and plays a prominent role in physio-pathological processes such as inflammation, angiogenesis and tissue fibrosis. In addition to the binding to its cognate receptors CXCR4 and CXCR7, CXCL12 interacts with heparan-sulfates (HS) which coordinate its biological activity. We have previously highlighted the essential role of CXCL12/HS interactions in vascular growth and remodeling in the setting of critical limb ischemia. In addition, studies in experimental model of MI revealed a protective role for the CXCL12α isoform, through the regulation of cardiomyocyte survival and recruitment of inflammatory cells. However, in mice, three CXCL12 isoforms (α, β and γ) have been identified and, among them, the CXCL12γ isoform shows an unchallenged ability to cooperate with HS, suggesting a putative pivotal role in tissue repair. Objectives The aim of the study is to analyze the role of CXCL12γ isoform and the importance of CXCL12/HS interactions in post-ischemic cardiac remodeling in an acute model of MI. Methods MI was induced by permanent ligation of the left ascending coronary artery in mice carrying a Cxcl12 gene mutation that precludes interactions with HS (Cxcl12Gagtm) and in Cxcl12γ knock-in animals (Cxcl12γ-KI) harboring CXCL12γ deficiency. Alternatively, the impact of CXCL12γ overexpression and the importance of its interactions with HS was also evaluated in wild-type (WT) mice receiving transcutaneous echo-guided injections of adenovirus encoding WT Cxcl12γ or HS-binding-disabled Cxcl12γ in cardiac tissue. Cardiac function and remodeling have been assessed through echocardiography analysis, evaluation of infarct size, interstitial fibrosis, vascular growth (capillary and arteriole densities) and inflammatory cell infiltration into the cardiac tissue. Results After MI, Cxcl12Gagtm and Cxcl12γ-KI ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/eurheartj/ehz746.0890 |
| الاتاحة: | https://doi.org/10.1093/eurheartj/ehz746.0890 http://academic.oup.com/eurheartj/article-pdf/40/Supplement_1/ehz746.0890/30201203/ehz746.0890.pdf |
| Rights: | https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model |
| رقم الانضمام: | edsbas.C327352B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/eurheartj/ehz746.0890 |
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