Increased fibulin-5 and elastin in S100A4/Mts1 mice with pulmonary hypertension.

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 Res

journal_title

Circulation research

authors

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 M

doi

10.1161/01.RES.0000182425.49768.8a

subject

Has Abstract

pub_date

2005-09-16 00:00:00

pages

596-604

issue

6

eissn

0009-7330

issn

1524-4571

pii

01.RES.0000182425.49768.8a

journal_volume

97

pub_type

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