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Heme Oxygenase-1 Expression Affects Murine Abdominal Aortic Aneurysm Progression
Junya Azuma1, Ronald J Wong2, Takeshi Morisawa2
1Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, United States of America.
Plos One
|February 20, 2016
Summary
Heme oxygenase-1 (HO-1) deficiency worsens abdominal aortic aneurysm (AAA) development. Inducing HO-1, via heme or statins, may offer a new therapeutic strategy for preventing AAA disease.
Area of Science:
- Vascular Biology
- Enzymology
- Immunology
Background:
- Heme oxygenase-1 (HO-1) is a cytoprotective enzyme in the vasculature.
- Reduced HO-1 expression is linked to abdominal aortic aneurysm (AAA) development.
- Heme strongly induces HO-1 expression.
Purpose of the Study:
- To investigate the role of HO-1 deficiency in AAA development.
- To explore therapeutic strategies for AAA prevention by targeting HO-1.
Main Methods:
- Utilized porcine pancreatic elastase (PPE) and Angiotensin II (Ang II) models of AAA in mice.
- Assessed AAA development in HO-1 heterozygous mice.
- Analyzed cytokine expression in peritoneal macrophages.
- Investigated the effects of heme and rosuvastatin treatment.
Main Results:
- HO-1 deficiency augmented AAA development and promoted pro-inflammatory cytokine expression.
- Heme treatment normalized AAA progression in HO-1 deficient mice.
- Rosuvastatin induced HO-1 expression and suppressed AAA progression independently of lipid lowering.
Conclusions:
- HO-1 plays a critical protective role in AAA pathogenesis.
- Targeting HO-1 induction represents a potential therapeutic strategy for AAA prevention.
- Pleiotropic effects of statins, like HO-1 upregulation, may benefit AAA patients.
