Journal
AMERICAN JOURNAL OF HYPERTENSION
Volume 28, Issue 4, Pages 518-526Publisher
OXFORD UNIV PRESS
DOI: 10.1093/ajh/hpu194
Keywords
12/15-lipoxygenase; angiotensin II; baicalein; blood pressure; cardiac remodeling; hyper tension; signaling pathways
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Funding
- 973 program [2012CB517802]
- National Natural Science Foundation of China [81025001, 81330003]
- Chang Jiang Scholar Program
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BACKGROUND Baicalein, a specific lipoxygenase (LOX) inhibitor, has anti-inflammatory and antioxidant effects. However, the functional role of baicalein in angiotensin II (Ang II)-induced hypertension and cardiac remodeling remains unclear. Here we investigated the effect of baicalein on cardiac hypertrophy and fibrosis and the underlying mechanism. METHODS Wild-type (WT) mice were injected with Ang II (1,200 ng/kg/min) alone or together with 12/15-LOX inhibitor baicalein (25 mg/kg) for 14 days. Histological examinations were performed on heart sections with hematoxylin and eosin, Masson's trichrome, wheat germ agglutinin staining, and immunohistochemistry. The messenger RNA (mRNA) expression of cytokines and protein levels were detected by real-time polymerase chain reaction (PCR) and western blot analysis respectively. RESULTS Ang II infusion significantly increased blood pressure but decreased cardiac contractile function reflected by fractional shortening% and ejection fraction% compared with saline-treated mice. Moreover, Ang II infusion resulted in marked cardiac hypertrophy and fibrosis, promoted accumulation of macrophages and T cells, the expression of proinflammatory cytokines and malondialdehyde (MDA) production. However, these actions were markedly reversed by administration of baicalein in mice. Mechanistically, the protective effects of baicalein were associated with the inhibition of inflammation, oxidative stress, and multiple signaling pathways (AKT/mTOR, ERK1/2, nuclear factor-kappa B (NF-kappa B), and calcineurin) in the Ang II-treated mice. CONCLUSIONS This study demonstrates that baicalein can significantly ameliorate Ang II-induced hypertension and cardiac remodeling, and may be a novel therapeutic drug for prevention of hypertensive heart diseases.
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