Deficiency of MAPK-activated protein kinase 2 (MK2) prevents adverse remodelling and promotes endothelial healing after arterial injury

Thromb Haemost. 2014 Dec;112(6):1264-76. doi: 10.1160/TH14-02-0174. Epub 2014 Aug 14.


Maladaptive remodelling of the arterial wall after mechanical injury (e. g. angioplasty) is characterised by inflammation, neointima formation and media hypertrophy, resulting in narrowing of the affected artery. Moreover, mechanical injury of the arterial wall causes loss of the vessel protecting endothelial cell monolayer. Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2), a major downstream target of p38 MAPK, regulates inflammation, cell migration and proliferation, essential processes for vascular remodelling and re-endothelialisation. Therefore, we investigated the role of MK2 in remodelling and re-endothelialisation after arterial injury in genetically modified mice in vivo. Hypercholesterolaemic low-density-lipoprotein-receptor-deficient mice (ldlr-/-) were subjected to wire injury of the common carotid artery. MK2-deficiency (ldlr-/-/mk2-/-) nearly completely prevented neointima formation, media hypertrophy, and lumen loss after injury. This was accompanied by reduced proliferation and migration of MK2-deficient smooth muscle cells. In addition, MK2-deficiency severely reduced monocyte adhesion to the arterial wall (day 3 after injury, intravital microscopy), which may be attributed to reduced expression of the chemokine ligands CCL2 and CCL5. In line, MK2-deficiency significantly reduced the content of monocytes, neutrophiles and lymphocytes of the arterial wall (day 7 after injury, flow cytometry). In conclusion, in a model of endothelial injury (electric injury), MK2-deficiency strongly increased proliferation of endothelial cells and improved re-endothelialisation of the arterial wall after injury. Deficiency of MK2 prevents adverse remodelling and promotes endothelial healing of the arterial wall after injury, suggesting that MK2-inhibition is a very attractive intervention to prevent restenosis after percutaneous therapeutic angioplasty.

Keywords: Arterial remodelling; MK2; inflammation; leukocytes; reendothelialisation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carotid Artery Injuries / enzymology*
  • Carotid Artery Injuries / genetics
  • Carotid Artery Injuries / pathology
  • Carotid Artery, Common / enzymology*
  • Carotid Artery, Common / pathology
  • Cell Adhesion
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Chemokine CCL2 / metabolism
  • Chemokine CCL5 / metabolism
  • Disease Models, Animal
  • Endothelium, Vascular / enzymology*
  • Endothelium, Vascular / injuries
  • Endothelium, Vascular / pathology
  • Hypercholesterolemia / complications
  • Hypercholesterolemia / genetics
  • Hypercholesterolemia / metabolism
  • Hyperplasia
  • Inflammation / enzymology
  • Inflammation / pathology
  • Inflammation / prevention & control
  • Intracellular Signaling Peptides and Proteins / deficiency*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Leukocytes / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / pathology
  • Neointima
  • Protein-Serine-Threonine Kinases / deficiency*
  • Protein-Serine-Threonine Kinases / genetics
  • Re-Epithelialization
  • Receptors, LDL
  • Vascular Remodeling*
  • Wound Healing*


  • Ccl2 protein, mouse
  • Ccl5 protein, mouse
  • Chemokine CCL2
  • Chemokine CCL5
  • Intracellular Signaling Peptides and Proteins
  • Receptors, LDL
  • MAP-kinase-activated kinase 2
  • Protein-Serine-Threonine Kinases