Journal
INTERNATIONAL HEART JOURNAL
Volume 61, Issue 1, Pages 160-168Publisher
INT HEART JOURNAL ASSOC
DOI: 10.1536/ihj.19-096
Keywords
Seaweed polysaccharides; Pulmonary vascular remodeling; TGF-beta 1; Oxidative stress; Inflammatory cytokine
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Funding
- National Natural Science of China (NSFC) [31640050, 31571829]
- Natural Science Foundation of Shandong Province [ZR2016HQ23]
- China Postdoctoral Science Foundation [2018M630757]
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Pulmonary arterial hypertension (PAH) is a serious and fatal cardiovascular disorder characterized by increased pulmonary vascular resistance and progressive pulmonary vascular remodeling. The underlying pathological mechanisms of PAH are multi-factorial and multi-cellular. Alginate oligosaccharide (AOS), which is produced by depolymerizing alginate, shows better pharmacological activities and beneficial effects. The present study was undertaken to investigate the effects and potential mechanisms of AOS-mediated alleviation of pulmonary hypertension. Pulmonary hypertension was induced in Sprague-Dawley rats by a single intraperitoneal injection of monocrotaline (MCT; 60 mg/kg). Five weeks after the injection of MCT, AOS (5, 10, and 20 mg.kg(-1).d(-1)) was injected intraperitoneally for another three weeks. The results showed that AOS prevented the development of MCT-induced pulmonary hypertension and right ventricular hypertrophy in a dose-dependent manner. AOS treatment also prevented MCT-induced pulmonary vascular remodeling via inhibition of the TGF-beta 1/p-Smad2 signaling pathway. Furthermore, AOS treatment downregulated the expression of malondialdehyde, nicotinainide adenine dinucleotide phosphate oxidase, and pro-inflammatory cytokines, decreased macrophage infiltration, and upregulated the expression of anti-inflammatory cytokines. These findings indicate that AOS exerts anti-oxidative and anti-inflammatory effects in pulmonary arteries, which may contribute to the alleviation of pulmonary hypertension and pulmonary vascular remodeling.
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