Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-2-15
pubmed:abstractText
Vascular expression of bone morphogenetic type IA receptor (Bmpr1a) is reduced in lungs of patients with pulmonary arterial hypertension, but the significance of this observation is poorly understood. To elucidate the role of Bmpr1a in the vascular pathology of pulmonary arterial hypertension and associated right ventricular (RV) dysfunction, we deleted Bmpr1a in vascular smooth muscle cells and in cardiac myocytes in mice using the SM22alpha;TRE-Cre/LoxP;R26R system. The LacZ distribution reflected patchy deletion of Bmpr1a in the lung vessels, aorta, and heart of SM22alpha;TRE-Cre;R26R;Bmpr1a(flox/+) and flox/flox mutants. This reduction in BMPR-IA expression was confirmed by Western immunoblot and immunohistochemistry in the flox/flox group. This did not affect pulmonary vasoreactivity to acute hypoxia (10% O2) or the increase in RV systolic pressure and RV hypertrophy following 3 weeks in chronic hypoxia. However, both SM22alpha;TRE-Cre;R26R;Bmpr1a(flox/+) and flox/flox mutant mice had fewer muscularized distal pulmonary arteries and attenuated loss of peripheral pulmonary arteries compared with age-matched control littermates in hypoxia. When Bmpr1a expression was reduced by short interference RNA in cultured pulmonary arterial smooth muscle cells, serum-induced proliferation was attenuated explaining decreased hypoxia-mediated muscularization of distal vessels. When Bmpr1a was reduced in cultured microvascular pericytes by short interference RNA, resistance to apoptosis was observed and this could account for protection against hypoxia-mediated vessel loss. The similar elevation in RV systolic pressure and RV hypertrophy, despite the attenuated remodeling with chronic hypoxia in the flox/flox mutants versus controls, was not a function of elevated left ventricular end diastolic pressure but was associated with increased periadventitial deposition of elastin and collagen, potentially influencing vascular stiffness.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-10608876, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-10712517, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-10772805, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-10969033, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-11399703, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-11416217, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-11684638, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-11799142, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-11815437, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-11854453, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-11857780, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-11997476, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-12444028, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-12525995, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-12571257, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-12690034, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-12895029, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-12963706, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-14746809, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-15031260, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-15194174, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-15286002, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-15528223, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-15863631, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-15883158, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-16027259, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-16037571, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-16100039, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-16109920, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-16361357, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-16497988, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-1836309, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-1928407, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-3161000, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-443445, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-7624392, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-7657163, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-8543149, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-8692238, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-8915187, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-9124602, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-9420335, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-9575947, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-9576110, http://linkedlifedata.com/resource/pubmed/commentcorrection/18079409-9916792
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
102
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
380-8
pubmed:dateRevised
2011-2-9
pubmed:meshHeading
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