Soluble receptor for advanced glycation end products (sRAGE) attenuates haemodynamic changes to chronic hypoxia in the mouse
| Autor: | Kirsty M. Mair, Simon Kennedy, Marie-Ann Ewart, David G.S. Farmer |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine Serotonin medicine.medical_specialty Contraction (grammar) Hypertension Pulmonary Receptor for Advanced Glycation End Products Pulmonary Artery Vascular Remodeling Cell Line Vascular remodelling in the embryo Mice Cricetulus Glycation Cricetinae Internal medicine medicine Animals Pharmacology (medical) Hypoxia Receptor Cell Proliferation Lung Chemistry Biochemistry (medical) Hemodynamics Fibroblasts Hypoxia (medical) medicine.disease Pulmonary hypertension Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Endocrinology Ventricular pressure medicine.symptom Muscle Contraction |
| Zdroj: | Pulmonary Pharmacology & Therapeutics. 29:7-14 |
| ISSN: | 1094-5539 |
| DOI: | 10.1016/j.pupt.2014.01.002 |
| Popis: | The calgranulin-like protein MTS1/S100A4 and the receptor for advanced glycation end-products (RAGE) have recently been implicated in mediating pulmonary arterial smooth muscle cell proliferation and vascular remodelling in experimental pulmonary arterial hypertension (PH). Here, the effects of RAGE antagonism upon 2 weeks of hypobaric hypoxia (10% O2)-induced PH in mice were assessed. Treatment with sRAGE was protective against hypobaric hypoxia-induced increases in right ventricular pressure but distal pulmonary vascular remodelling was unaffected. Intralobar pulmonary arteries from hypobaric hypoxic mice treated with sRAGE showed protection against a hypoxia-induced reduction in compliance. However, a combination of sRAGE and hypoxia also dramatically increased the force of contractions to KCl and 5-HT observed in these vessels. The acute addition of sRAGE to the organ bath produced a small, sustained contraction in intralobar pulmonary vessels and produced a synergistic enhancement of the maximal force of contraction in subsequent concentration-response curves to 5-HT. sRAGE had no effect on 5-HT-induced proliferation of Chinese hamster lung fibroblasts (CCL39), used since they have a similar pharmacological profile to mouse pulmonary fibroblasts but, surprisingly, produced a marked increase in hypoxia-induced proliferation. These data implicate RAGE as a modulator of both vasoreactivity and of proliferative processes in the response of the pulmonary circulation to chronic-hypoxia. |
| Databáze: | OpenAIRE |
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