Selective Stimulation of Cardiac Lymphangiogenesis Reduces Myocardial Edema and Fibrosis Leading to Improved Cardiac Function Following Myocardial Infarction

• DOI: 10.1161/circulationaha.115.020143
• Publication Date: 2016-03-02T03:53:22Z
• Authors: Orianne Henri; Chris Pouehe; Mahmoud Houssari; Ludovic Galas; Lionel Nicol; Florence Edwards-...; Jean-Paul Henry; Anais Dumesnil; Inès Boukhalfa; Sébastien Banquet; Damien Schapman; Christian Thuillez; Vincent Richard; Paul Mulder; Ebba Brakenhielm
• Keywords: Lymphangiogenesis; Cardiac Fibrosis; Endothelial Dysfunction

Background— The lymphatic system regulates interstitial tissue fluid balance, and malfunction causes edema. heart has an extensive network displaying a dynamic range of lymph flow in physiology. Myocardial edema occurs many cardiovascular diseases, eg, myocardial infarction (MI) chronic failure, suggesting that cardiac transport may be insufficient pathology. Here, we investigate rats the impact MI subsequent failure on network. Further, evaluate for first time functional effects selective therapeutic stimulation lymphangiogenesis post-MI. Methods Results— We investigated structure function with induced by either temporary occlusion (n=160) or permanent ligation (n=100) left coronary artery. Although robust, intramyocardial capillary lymphangiogenesis, adverse remodeling epicardial precollector collector lymphatics occurred, leading to reduced capacity. Consequently, persisted several months post-MI, extending from infarct noninfarcted myocardium. Intramyocardial-targeted delivery vascular endothelial growth factor receptor 3–selective designer protein VEGF-C C152S , using albumin-alginate microparticles, accelerated dose-dependent manner limited As result, balance was improved, inflammation, fibrosis, dysfunction were attenuated. Conclusions— show that, despite endogenous lymphangiogenic response collecting ducts contribute development inflammation-aggravating fibrosis dysfunction. Moreover, our data reveal promising new approach treatment diseases.