title: Bone marrow derived cells are involved in the pathogenesis of cardiac hypertrophy in response to pressure overload.
abstract: BACKGROUND
  Bone marrow (BM) cells possess broad differentiation potential and can form various cell lineages in response to pathophysiological cues. The present study investigated whether BM-derived cells contribute to the pathogenesis of cardiac hypertrophy, as well as the possible cellular mechanisms involved in such a role.
  
  
  RESULTS
  Lethally irradiated wild-type mice were transplanted with BM cells from enhanced green fluorescent protein-transgenic mice. The chimeric mice were subjected to either prolonged hypoxia or transverse aortic constriction. BM-derived enhanced green fluorescent protein-expressing cardiomyocytes increased in number over time, emerging predominantly in the pressure-overloaded ventricular myocardium, although they constituted <0.01% of recipient cardiomyocytes. To determine whether BM-derived cardiomyocytes were derived from cell fusion or transdifferentiation at the single-cell level, lethally irradiated Cre mice were transplanted with BM cells from the double-conditional Cre reporter mouse line Z/EG. BM-derived cardiomyocytes were shown to arise from both cell fusion and transdifferentiation. Interestingly, BM-derived myofibroblasts expressing both vimentin and alpha-smooth muscle actin were concentrated in the perivascular fibrotic area. These cells initially expressed MAC-1/CD14 but lost expression of these markers during the chronic phase, which suggests that they were derived from monocytes. A similar phenomenon occurred in cultured human monocytes, most of which ultimately expressed vimentin and alpha-smooth muscle actin.
  
  
  CONCLUSIONS
  We found that BM-derived cells were involved in the pathogenesis of cardiac hypertrophy via the dual mechanisms of cell fusion and transdifferentiation. Moreover, the present results suggest that BM-derived monocytes accumulating in the perivascular space might play an important role in the formation of perivascular fibrosis via direct differentiation into myofibroblasts.
authors: Department of Regenerative Medicine and Advanced Cardiac Therapeutics, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Jin
authors: J
authors: Endo
authors: Motoaki
authors: M
authors: Sano
authors: Jun
authors: J
authors: Fujita
authors: Kentaro
authors: K
authors: Hayashida
authors: Shinsuke
authors: S
authors: Yuasa
authors: Naoki
authors: N
authors: Aoyama
authors: Yuji
authors: Y
authors: Takehara
authors: Osamu
authors: O
authors: Kato
authors: Shinji
authors: S
authors: Makino
authors: Satoshi
authors: S
authors: Ogawa
authors: Keiichi
authors: K
authors: Fukuda
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology*; D006332:Cardiomegaly / Q000209:etiology* / Q000473:pathology*; D002459:Cell Fusion / Q000379:methods; D002645:Chickens; D006976:Hypertension, Pulmonary / Q000150:complications / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000473:pathology