Abstract:
:Transgenic mice overexpressing the calcium binding protein, S100A4/Mts1, occasionally develop severe pulmonary vascular obstructive disease. To understand what underlies this propensity, we compared the pulmonary vascular hemodynamic and structural features of S100A4/Mts1 with control C57Bl/6 mice at baseline, following a 2-week exposure to chronic hypoxia, and after 1 and 3 months "recovery" in room air. S100A4/Mts1 mice had greater right ventricular systolic pressure and right ventricular hypertrophy at baseline, which increased further with chronic hypoxia and was sustained after 3 months "recovery" in room air. These findings correlated with a heightened response to acute hypoxia and failure to vasodilate with nitric oxide or oxygen. S100A4/Mts1 mice, when compared with C57Bl/6 mice, also had impaired cardiac function judged by reduced ventricular elastance and decreased cardiac output. Despite higher right ventricular systolic pressures with chronic hypoxia, S100A4/Mts1 mice did not develop more severe PVD, but in contrast to C57Bl/6 mice, these features did not regress on return to room air. Microarray analysis of lung tissue identified a number of genes differentially upregulated in S100A4/Mts1 versus control mice. One of these, fibulin-5, is a matrix component necessary for normal elastin fiber assembly. Fibulin-5 was localized to pulmonary arteries and associated with thickened elastic laminae. This feature could underlie attenuation of pulmonary vascular changes in response to elevated pressure, as well as impaired reversibility.
journal_name
Circ Resjournal_title
Circulation researchauthors
Merklinger SL,Wagner RA,Spiekerkoetter E,Hinek A,Knutsen RH,Kabir MG,Desai K,Hacker S,Wang L,Cann GM,Ambartsumian NS,Lukanidin E,Bernstein D,Husain M,Mecham RP,Starcher B,Yanagisawa H,Rabinovitch Mdoi
10.1161/01.RES.0000182425.49768.8asubject
Has Abstractpub_date
2005-09-16 00:00:00pages
596-604issue
6eissn
0009-7330issn
1524-4571pii
01.RES.0000182425.49768.8ajournal_volume
97pub_type
杂志文章abstract::Mechanisms of denervation supersensitivity to sympathomimetic amines were studied in conscious animals. Norepinephrine, 0.1 micrograms/kg, increased left ventricular dP/dt significantly more (4208 +/- 828 mm Hg/sec) in dogs with cardiac denervation than in intact dogs (1029 +/- 280 mm Hg/sec), P less than 0.01, wherea...
journal_title:Circulation research
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更新日期:2007-09-28 00:00:00
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更新日期:1976-06-01 00:00:00
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更新日期:1995-05-01 00:00:00
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更新日期:2007-11-26 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.40.4.390
更新日期:1977-04-01 00:00:00
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pub_type: 杂志文章
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更新日期:1990-05-01 00:00:00
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更新日期:1979-02-01 00:00:00
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更新日期:1993-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.304899
更新日期:2015-02-13 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.73.5.839
更新日期:1993-11-01 00:00:00
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doi:10.1161/01.res.65.4.955
更新日期:1989-10-01 00:00:00
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更新日期:2020-01-03 00:00:00
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pub_type: 杂志文章
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更新日期:1998-06-01 00:00:00
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pub_type: 杂志文章
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更新日期:1991-11-01 00:00:00
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pub_type: 杂志文章
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更新日期:1994-10-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:2015-09-25 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2020-02-14 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.64.6.1127
更新日期:1989-06-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.52.4.423
更新日期:1983-04-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.43.5.738
更新日期:1978-11-01 00:00:00