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Angiotensin II depletes the skeletal muscle satellite cell pool and prevents skeletal muscle regeneration
Author(s) -
Yoshida Tadashi,
Galvez Sarah,
Rezk Bashir M.,
Semprun-Prieto Laura,
Sukhanov Sergiy,
Yablonka-Reuveni Zipora,
Delafontaine Patrice
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1078.7
Subject(s) - myod , skeletal muscle , myf5 , medicine , endocrinology , angiotensin ii , myocyte , angiotensin ii receptor type 1 , biology , chemistry , myogenesis , receptor
Chronic conditions such as congestive heart failure or end‐stage renal disease are characterized by increased angiotensin II (Ang II) and cachexia and we have shown that Ang II infusion in rodents causes sustained skeletal muscle wasting. To determine potential effects of Ang II on muscle regeneration we infused C57BL/6 mice with Ang II together with skeletal muscle injection of cardiotoxin (CTX). Ang II reduced the number of regenerating myofibers compared to CTX injected sham‐infused control (67.7% decrease at day 7, p<0.01), suggesting that Ang II prevents muscle regeneration. Ang II reduced myofiber‐associated satellite cells (SCs) in Myf5 nLacZ/+ mice. Ang II reduced the number of SCs (CD45 − /Sca‐1 − /CD11b − /CD31 − /CD34 + /Integrin‐α7 + population by FACS) and this effect was blocked by candesartan, a specific AT1 receptor blocker, and in AT1aR −/− mice. Quantitative PCR on sorted SCs and FACS analysis showed the high expression of AT1R in SCs compared to myofibers or interstitial cells, suggesting that Ang II directly acts on SCs to reduce their number. Ang II reduced the SC proliferation marker MyoD in vivo , and Ang II dose‐dependently decreased MyoD expression in SC culture in vitro . These data suggest that Ang II signals via the AT1aR on SCs and prevents SC proliferation via suppression of MyoD expression, thereby inhibiting normal skeletal muscle regeneration. This study was supported by grants from the National Institutes of Health/National Heart, Lung and Blood Institute (R01HL080682 and R01HL070241).