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Improved heart function follows enhanced inflammatory cell recruitment and angiogenesis in 11 beta HSD1-deficient mice post-MI

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    Rights statement: © The Author 2010. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits noncommercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

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Original languageEnglish
Pages (from-to)159-167
Number of pages9
JournalCardiovascular Research
Issue number1
Publication statusPublished - Oct 2010


Aims Mice unable to locally regenerate corticosterone due to deficiency of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) have enhanced angiogenesis during acute myocardial infarct healing. The present study investigates the hypotheses that in these mice (i) inflammation and angiogenic signalling are promoted and (ii) longer-term remodelling and function are improved.

Methods and results Myocardial infarction (MI) was induced by coronary artery ligation in 11βHSD1−/− and wild-type (C57BL/6) mice. Studies were terminated 2, 4, 7, and 28 days post-surgery. Increased vessel density (CD31 immunoreactivity) on the infarct border was confirmed 7 days after MI in 11βHSD1−/− hearts (P < 0.05) and was accompanied by improved ejection fraction (ultrasound) compared with C57BL/6. During wound healing, recruitment of neutrophils (at 2 days after MI) and macrophages (from 4 days after MI) and expression of monocyte-chemoattractant protein-1 was increased in 11βHSD1−/− compared with C57BL/6 hearts (P< 0.05). Recruitment of alternatively activated YM1-positive macrophages was particularly enhanced in the period preceding increased vessel density and was accompanied by increased expression of pro-angiogenic IL-8. By 28 days post-MI, when the infarct scar had matured, higher vessel density was maintained in 11βHSD1−/− hearts and vessels were smooth-muscle coated. Infarct scars were thicker (P < 0.001) in 11βHSD1−/−compared with C57BL/6 hearts and ejection fraction was higher (P < 0.05).

Conclusion Increased vessel density in healing infarcts of mice deficient in 11−/−HSD1 follows recruitment of pro-reparative macrophages and increased pro-angiogenic signalling. Mature infarcts show less thinning and cardiac function is improved relative to wild-type mice, suggesting that 11βHSD1 may be a novel therapeutic target after MI.

    Research areas

  • Angiogenesis , Inflammation, Alternatively activated macrophages , YM1, IL-8

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