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Hypoxia‐Induced Pulmonary Hypertension: Possible Loss of Caveolin‐1 Function
Author(s) -
Mathew Rajamma,
Huang Jing,
Gewitz Michael H
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1034.4
Subject(s) - hypoxia (environmental) , pulmonary hypertension , cardiology , medicine , chemistry , oxygen , organic chemistry
We have previously shown an early and progressive IL‐6 mRNA upregulation, IL‐6 bioactivity, loss of endothelial caveolin‐1 and reciprocal activation of PY‐STAT3, and subsequent loss of HSP90 and eNOS in an inflammatory (monocrotaline, MCT) model of pulmonary hypertension (PH) in rats. Furthermore, rescue of caveolin‐1 inhibits PY‐STAT3 activation and attenuates MCT‐induced PH. Since hypoxia also elicits an inflammatory response, we investigated time‐dependent alterations in the expression of caveolin‐1, PY‐STAT3, eNOS and HSP90 during hypoxia‐induced PH. Male Sprague‐Dawley rats were subjected to hypobaric hypoxia and examined at 48h, 1 and 2 weeks of hypoxia. Significant PH was noted at 1 and 2 wks, and RVH at 2 wks of hypoxia. PY‐STAT3 activation was observed at 48 hrs before the onset of PH, which was persistent, but there was no loss of caveolin‐1 expression during hypoxia. Expression of eNOS was significantly increased during hypoxia; however the p‐eNOS was decreased at 2 wks after a slight increase at 48h and 1 wk of hypoxia. HSP90 expression was unaltered. Caveolin‐1 is known to inhibit PY‐STAT3 activation and modulate eNOS activation. These results suggest that caveolin‐1 dysfunction may play a significant role in hypoxia‐induced PH.