n/a
Abstract Title:

Evidence for Fucoidan-P-selectin Axis as a Therapeutic Target on Hypoxia-induced Pulmonary Hypertension.

Abstract Source:

Am J Respir Crit Care Med. 2018 Dec 17. Epub 2018 Dec 17. PMID: 30557519

Abstract Author(s):

Tatyana Novoyatleva, Baktybek Kojonazarov, Andreas Owczarek, Swathi Veeroju, Nabham Rai, Ingrid Henneke, Mario Böhm, Friedrich Grimminger, Hossein A Ghofrani, Werner Seeger, Norbert Weissmann, Ralph T Schermuly

Article Affiliation:

Tatyana Novoyatleva

Abstract:

RATIONALE: Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling and excessive proliferation of pulmonary artery smooth muscle cells (PASMCs). Fucoidan, polysacharidic ligand of an adhesion molecule P-selectin exhibits anti-proliferative properties. The effects of Fucoidan/P-selectin axis on vascular remodeling and pulmonary hypertension (PH) following hypoxia remain unexplored.

OBJECTIVES: We aimed to evaluate the therapeutic potential of targeting the fucoidan/P-selectin axis in PH.

METHODS: Mice with PH induced by chronic hypoxia (35 days) were given either fucoidan (from Fucus vesiculosus) or anti-P-selectin antibody (Rb40.34) during days 21-35. Right ventricular (RV) function was determined by echocardiography. Vascular morphometry was assessed by immunohistochemistry. Human and experimental PH lungs and PASMCs were used for assessment of P-selectin expression and function.

MEASUREMENTS AND MAIN RESULTS: Fucoidan attenuated chronic hypoxia-induced PH in mice, reducing pulmonary vascular remodelling and restoring RV function. In vitro, fucoidan inhibited hypoxia and growth factor stimulated PASMC proliferation and migration. Chronic hypoxia caused an up-regulation of P-selectin in the medial layer of small pulmonary arteries. P-selectin is persistently upregulated in PASMCs of human and hypoxia-induced experimental PH. HIF-1α directly bound to P-selectin promoter, transcriptionally activated P-selectin in hypoxia. P-selectin blockage resulted in a marked reduction of PASMCs proliferation in vitro. Blockage of P-selectin by administration of anti-P-selectin Rb40.34 antibody and P-selectin deficient mice improved vascular remodelling and restored RV function.

CONCLUSIONS: Fucoidan is a potent natural adjuvant representing a promising therapeutic approach for PH. Our data indicate a previously unrecognized role of P-selectin in proliferative response of PASMCs associated with PH.

Study Type : In Vitro Study

Print Options


Key Research Topics

Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

500+ pages of Natural Medicine Alternatives and Information.

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2020 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.