title: Normal endothelial but impaired arterial development in MAP-Kinase activated protein kinase 2 (MK2) deficient mice.
abstract: Angiogenesis is a fundamental process during development and disease, and many details of the underlying molecular and cellular mechanisms are incompletely understood. Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2), a major downstream target of p38 MAPK, has recently been identified as a regulator of Interleukin 1β dependent angiogenesis in vivo, and in vitro data suggest a role of MK2 for VEGF-dependent angiogenic processes in endothelial cells. We thus hypothesized that MK2 plays a role during physiological vascular development in vivo. Vascular development was investigated in the retina of MK2-deficient mice. Retinal angiogenesis such as sprouting, branching and pruning was unchanged in MK2-/-mice compared to wildtype littermates. Early arterial development was also comparable between genotypes. However, with further expansion of vascular smooth muscle cells (SMC) during maturation of the arterial network at later time points, the number of arterial branch points was significantly lower in MK2-/-mice, resulting in a reduced total arterial area in adult mice. Isolated aortic smooth muscle cells from MK2-/-mice showed a more dedifferentiated phenotype in vitro and downregulation of central SMC marker genes, consistent with the known impaired migration of MK2-/-SMC. In conclusion, MK2 is not required for physiological retinal angiogenesis. However, its loss is associated with an altered genetic profile of SMC and an impaired arterial network in adult mice, indicating a distinct and probably cell-specific role of MK2 in arteries.
authors: Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors: L Christian
authors: LC
authors: Napp
authors: Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors: Olga
authors: O
authors: Jabs
authors: Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors: Anna
authors: A
authors: Höckelmann
authors: Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors: Jochen
authors: J
authors: Dutzmann
authors: Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors: Piyush R
authors: PR
authors: Kapopara
authors: Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors: Daniel G
authors: DG
authors: Sedding
authors: Department of Biochemistry, Hannover Medical School, Hannover, Germany.
authors: Matthias
authors: M
authors: Gaestel
authors: Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors: Johann
authors: J
authors: Bauersachs
authors: Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors: Udo
authors: U
authors: Bavendiek
keywords: Angiogenesis; Arteriogenesis; Branching; MAP-Kinase; MK2; Sprouting