HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Am J Physiol Cell Physiol 292: C953-C967, 2007. First published October 4, 2006; doi:10.1152/ajpcell.00154.2006
0363-6143/07 $8.00

This Article Free upon publication Full Text Full Text (PDF) All Versions of this Article: 292/2/C953    most recent 00154.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Contreras-Shannon, V. Articles by Shireman, P. K. Search for Related Content PubMed PubMed Citation Articles by Contreras-Shannon, V. Articles by Shireman, P. K.

MUSCLE CELL BIOLOGY AND CELL MOTILITY

Fat accumulation with altered inflammation and regeneration in skeletal muscle of CCR2–/– mice following ischemic injury

Departments of ¹Surgery, ²Epidemiology and Biostatistics, ³Pathology, ⁴Periodontics and ⁵Medicine, ⁶Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio; ⁷Protein Design Labs, Fremont, California; and ⁸The South Texas Veterans Health Care System, San Antonio, Texas

Submitted 5 April 2006 ; accepted in final form 27 September 2006

Chemokines recruit inflammatory cells to sites of injury, but the role of the CC chemokine receptor 2 (CCR2) during regenerative processes following ischemia is poorly understood. We studied injury, inflammation, perfusion, capillary formation, monocyte chemotactic protein-1 (MCP-1) levels, muscle regeneration, fat accumulation, and transcription factor activation in hindlimb muscles of CCR2–/– and wild-type (WT) mice following femoral artery excision (FAE). In both groups, muscle injury and restoration of vascular perfusion were similar. Nevertheless, edema and neutrophil accumulation were significantly elevated in CCR2–/– compared with WT mice at day 1 post-FAE and fewer macrophages were present at day 3. MCP-1 levels in post-ischemic calf muscle of CCR2–/– animals were significantly elevated over baseline through 14 days post-FAE and were higher than WT mice at days 1, 7, and 14. In addition, CCR2–/– mice exhibited impaired muscle regeneration, decreased muscle fiber size, and increased intermuscular adipocytes with similar capillaries/mm² postinjury. Finally, the transcription factors, MyoD and signal transducers of and activators of transcription-3 (STAT3), were significantly increased above baseline but did not differ significantly between groups at any time point post-FAE. These findings suggest that increases in MCP-1, and possibly, MyoD and STAT3, may modulate molecular signaling in CCR2–/– mice during inflammatory and regenerative events. Furthermore, alterations in neutrophil and macrophage recruitment in CCR2–/– mice may critically alter the normal progression of downstream regenerative events in injured skeletal muscle and may direct myogenic precursor cells in the regenerating milieu toward an adipogenic phenotype.

adipocyte; macrophage; MyoD; myogenic progenitor cell; neutrophil; signal transducers of and activators of transcription-3

This article has been cited by other articles:

				B. J. Capoccia, A. D. Gregory, and D. C. Link Recruitment of the inflammatory subset of monocytes to sites of ischemia induces angiogenesis in a monocyte chemoattractant protein-1-dependent fashion J. Leukoc. Biol., September 1, 2008; 84(3): 760 - 768. [Abstract] [Full Text] [PDF]

				M. J. Zhu, B. Han, J. Tong, C. Ma, J. M. Kimzey, K. R. Underwood, Y. Xiao, B. W. Hess, S. P. Ford, P. W. Nathanielsz, et al. AMP-activated protein kinase signalling pathways are down regulated and skeletal muscle development impaired in fetuses of obese, over-nourished sheep J. Physiol., May 15, 2008; 586(10): 2651 - 2664. [Abstract] [Full Text] [PDF]

				J.-S. Silvestre, Z. Mallat, A. Tedgui, and B. I. Levy Post-ischaemic neovascularization and inflammation Cardiovasc Res, May 1, 2008; 78(2): 242 - 249. [Abstract] [Full Text] [PDF]

				D. D Sin and W D. Reid Is inflammation good, bad or irrelevant for skeletal muscles in COPD? Thorax, February 1, 2008; 63(2): 95 - 96. [Full Text] [PDF]

				O. Ochoa, D. Sun, S. M. Reyes-Reyna, L. L. Waite, J. E. Michalek, L. M. McManus, and P. K. Shireman Delayed angiogenesis and VEGF production in CCR2 / mice during impaired skeletal muscle regeneration Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2007; 293(2): R651 - R661. [Abstract] [Full Text] [PDF]

				L. Arnold, A. Henry, F. Poron, Y. Baba-Amer, N. van Rooijen, A. Plonquet, R. K. Gherardi, and B. Chazaud Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis J. Exp. Med., May 14, 2007; 204(5): 1057 - 1069. [Abstract] [Full Text] [PDF]