JCI - Sonic hedgehog is a critical mediator of erythropoietin-induced cardiac protection in mice

Sonic hedgehog is a critical mediator of erythropoietin-induced cardiac protection in mice

Kazutaka Ueda, Hiroyuki Takano, Yuriko Niitsuma, Hiroshi Hasegawa, Raita Uchiyama, Toru Oka, Masaru Miyazaki, Haruaki Nakaya, Issei Komuro

Published in Volume 120, Issue 6

J Clin Invest. 2010; 120(6):2016–2029 doi:10.1172/JCI39896

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Figure 9

Cardiomyocyte-specific Shh deletion abolishes EPO-induced cardioprotection.

(A) Activation of Shh signaling after MI and EPO treatment. Hearts were treated with EPO or saline (control) and harvested 4 days (for Shh-N) or 7 days (for Patched) after MI (n = 4 for each). (B) Western blotting of Shh-N in the infarcted hearts from Shh-MerCre mice treated with or without tamoxifen. Mice were subjected to MI, treated with EPO, and sacrificed 4 days after MI (n = 4 for each condition). We measured LVEDD, FS, infarct size (C), the number of vessels, the ratio of vessels to cardiomyocyte, and the number of α-SMA–positive vessels (D) 14 days after MI (n = 8–14). *P < 0.05; ^#P < 0.01. (E and F) Western blotting of VEGF and qRT-PCR analysis of Ang-1 mRNA in the heart 7 days after MI. All mice were treated with EPO (n = 5). *P < 0.05. (G) Proposed mechanism underlying the cardioprotective effects of EPO during MI. The mechanisms denoted by the thicker lines are thought to be particularly important.