4.7 Review

Role of Cardiac Lymphatics in Myocardial Edema and Fibrosis JACC Review Topic of the Week

Journal

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Volume 76, Issue 6, Pages 735-744

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2020.05.076

Keywords

edema; fibrosis; inflammation; interstitial fluid pressure; lymphangiogenesis; VEGF-C

Funding

  1. European Research Area Network (ERA-NET) on Cardiovascular Diseases (ERA-Net-CVD) [LYMIT-DIS 2016]: Agence Nationale de la Recherche [ANR-16ECVD-0004]
  2. Instituto de Salud Carlos III [AC16/00020]
  3. FHU REMOD-VHF (INSERM laboratory) [U1096]
  4. French INSERM
  5. Normandy Region
  6. European Union: Europe gets involved in Normandie with European Regional Development Fund (ERDF): CPER/FEDER 2015 (DO-IT)
  7. CPER/FEDER 2016 (PACT-CBS)
  8. Spanish Ministry of Science, Innovation and Universities (Instituto de Salud Carlos III) [CIBERCV CB16/11/00483, PI18/01469]
  9. FEDER funds
  10. European Commission H2020 Programme [848109]

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The cardiac lymphatic network plays a key role in regulation of myocardial extracellular volume and immune cell homeostasis. In different pathological conditions cardiac lymphatics undergo significant remodeling, with insufficient lymphatic function and/or lymphangiogenesis leading to fluid accumulation and development of edema. Additionally, by modulating the reuptake of tissue-infiltrating immune cells, lymphatics regulate immune responses. Available evidence suggests that both edema and inadequate immune response resolution may contribute to extracellular matrix remodeling and interstitial myocardial fibrosis. Interestingly, stimulation of lymphangiogenesis has been shown to improve cardiac function and reduce the progression of myocardial fibrosis during heart failure development after myocardial infarction. This review goes through the available clinical and experimental data supporting a role for cardiac lymphatics in cardiac disease, focusing on the current evidence linking poor cardiac lymphatic transport to the fibrogenic process and discussing potential avenues for novel biomarkers and therapeutic targets to limit cardiac fibrosis and dysfunction. (C) 2020 by the American College of Cardiology Foundation.

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