Literature DB >> 18073453

Downregulation of angiopoietin-1 and Tie2 in chronic hypoxic pulmonary hypertension.

Akihito Yamamoto1, Hideki Takahashi, Yuko Kojima, Yasunari Tsuda, Yoshiteru Morio, Masashi Muramatsu, Yoshinosuke Fukuchi.   

Abstract

BACKGROUND: Angiopoietins, newly discovered vascular-specific growth factors, and vascular endothelial growth factors (VEGF) play distinct and complementary roles in angiogenesis and vascular maturation. However, the exact roles of angiogenic factors in the adult pulmonary vasculature remain unclear.
OBJECTIVE: To elucidate possible roles of angiopoietins and VEGF in the development of hypoxic pulmonary hypertension (PH), changes in the expression of angiogenic factors were examined.
METHODS: The cellular distribution and expression of angiopoietins and their receptor Tie2 and VEGF were investigated by RT-PCR, immunoblot, and immunohistochemical methods in rat lung under normal and hypoxic conditions.
RESULTS: During the development of PH with vascular remodeling characterized by a decrease in vessel density of intrapulmonary arteries, protein expression of angiopoietin-1 (Ang-1), Tie2, and VEGF significantly decreased in the pulmonary arteries, and Tie2 receptor was inactivated in the lung. The expression of angiopoietin-3 (Ang-3), an endogenous antagonist of Ang-1, significantly increased in the intima under hypoxic conditions.
CONCLUSIONS: Since both Ang-1/Tie2 and VEGF promote angiogenesis and vascular survival, and play protective roles in the adaptation of microvascular changes during the onset of PH, the downregulation of both Ang-1/Tie2 and VEGF and upregulation of Ang-3 appear to be associated with vascular rarefaction and the development of hypoxic PH. 2007 S. Karger AG, Basel

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Year:  2007        PMID: 18073453     DOI: 10.1159/000112432

Source DB:  PubMed          Journal:  Respiration        ISSN: 0025-7931            Impact factor:   3.580


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