title: The muscle contraction mode determines lymphangiogenesis differentially in rat skeletal and cardiac muscles by modifying local lymphatic extracellular matrix microenvironments.
abstract: OBJECTIVE
  Lymphatic vessels are of special importance for tissue homeostasis, and increases of their density may foster tissue regeneration. Exercise could be a relevant tool to increase lymphatic vessel density (LVD); however, a significant lack of knowledge remains to understand lymphangiogenesis in skeletal muscles upon training. Interestingly, training-induced lymphangiogenesis has never been studied in the heart. We studied lymphangiogenesis and LVD upon chronic concentric and chronic eccentric muscle contractions in both rat skeletal (Mm. Edl and Sol) and cardiac muscles.
  
  
  RESULTS
  We found that LVD decreased in both skeletal muscles specifically upon eccentric training, while this contraction increased LVD in cardiac tissue. These observations were supported by opposing local remodelling of lymphatic vessel-specific extracellular matrix components in skeletal and cardiac muscles and protein levels of lymphatic markers (Lyve-1, Pdpn, Vegf-C/D). Confocal microscopy further revealed transformations of lymphatic vessels into vessels expressing both blood (Cav-1) and lymphatic (Vegfr-3) markers upon eccentric training specifically in skeletal muscles. In addition and phenotype supportive, we found increased inflammation (NF-κB/p65, Il-1β, Ifn-γ, Tnf-α and MPO(+) cells) in eccentrically stressed skeletal, but decreased levels in cardiac muscles.
  
  
  CONCLUSIONS
  Our data provide novel mechanistic insights into lymphangiogenic processes in skeletal and cardiac muscles upon chronic muscle contraction modes and demonstrate that both tissues adapt in opposing manners specifically to eccentric training. These data are highly relevant for clinical applications, because eccentric training serves as a sufficient strategy to increase LVD and to decrease inflammation in cardiac tissue, for example in order to reduce tissue abortion in transplantation settings.
authors.affiliation: Department of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne, Cologne, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Greiwe
authors.affiliation: Department of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne, Cologne, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Vinck
authors.affiliation: Department of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne, Cologne, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Suhr
mesh_terms: D000818:Animals; D015153:Blotting, Western; D060833:Cellular Microenvironment / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D007150:Immunohistochemistry; D042583:Lymphangiogenesis / Q000502:physiology*; D042601:Lymphatic Vessels / Q000502:physiology; D018613:Microscopy, Confocal; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D009206:Myocardium; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
keywords: chronic training; concentric/eccentric contraction; extracellular matrix; inflammation; lymphatic vessel; skeletal/cardiac muscle