Abstract |
Erythropoietin reportedly has beneficial effects on the heart after myocardial infarction, but the underlying mechanisms of these effects are unknown. We here demonstrate that sonic hedgehog is a critical mediator of erythropoietin-induced cardioprotection in mice. Treatment of mice with erythropoietin inhibited left ventricular remodeling and improved cardiac function after myocardial infarction, independent of erythropoiesis and the mobilization of bone marrow-derived cells. Erythropoietin prevented cardiomyocyte apoptosis and increased the number of capillaries and mature vessels in infarcted hearts by upregulating the expression of angiogenic cytokines such as VEGF and angiopoietin-1 in cardiomyocytes. Erythropoietin also increased the expression of sonic hedgehog in cardiomyocytes, and inhibition of sonic hedgehog signaling suppressed the erythropoietin-induced increase in angiogenic cytokine expression. Furthermore, the beneficial effects of erythropoietin on infarcted hearts were abolished by cardiomyocyte-specific deletion of sonic hedgehog. These results suggest that erythropoietin protects the heart after myocardial infarction by inducing angiogenesis through sonic hedgehog signaling.
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Authors | Kazutaka Ueda, Hiroyuki Takano, Yuriko Niitsuma, Hiroshi Hasegawa, Raita Uchiyama, Toru Oka, Masaru Miyazaki, Haruaki Nakaya, Issei Komuro |
Journal | The Journal of clinical investigation
(J Clin Invest)
Vol. 120
Issue 6
Pg. 2016-29
(Jun 2010)
ISSN: 1558-8238 [Electronic] United States |
PMID | 20484812
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiogenesis Inducing Agents
- Angiopoietin-1
- Cytokines
- Hedgehog Proteins
- Recombinant Proteins
- Erythropoietin
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Topics |
- Angiogenesis Inducing Agents
(metabolism, pharmacology)
- Angiopoietin-1
(genetics, metabolism, pharmacology)
- Animals
- Apoptosis
(drug effects, genetics)
- Bone Marrow Cells
(metabolism, physiology)
- Capillaries
(metabolism, physiopathology)
- Cytokines
(genetics, metabolism, pharmacology)
- Erythropoietin
(genetics, metabolism, pharmacology)
- Hedgehog Proteins
(genetics, metabolism)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Myocardial Infarction
(genetics, metabolism, physiopathology)
- Myocytes, Cardiac
(drug effects, metabolism)
- Recombinant Proteins
- Signal Transduction
(drug effects, genetics)
- Up-Regulation
(drug effects)
- Ventricular Remodeling
(drug effects, genetics, physiology)
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