Mice lacking osteopontin exhibit increased left ventricular dilation and reduced fibrosis after aldosterone infusion.
BACKGROUND
Osteopontin, also known as cytokine Eta-1, plays an important role in postmyocardial infarction remodeling by regulating collagen accumulation. Aldosterone promotes collagen synthesis and structural remodeling of the heart. The role of osteopontin in aldosterone-induced fibrosis and myocardial remodeling is unknown. Osteopontin expression and left ventricular structural and functional remodeling were determined in wild-type and osteopontin knockout mice after aldosterone infusion.


RESULTS
Immunohistochemical analyses showed increased interstitial osteopontin protein in the wild-type left ventricle after 7 days of aldosterone infusion. After 4 weeks of aldosterone infusion, heart rate was unchanged, and there were similar increases in blood pressure (BP) and heart-to-body weight ratio in both wild-type and knockout mice. Left ventricular end-diastolic diameter was significantly higher, whereas percent fractional shortening was significantly lower (P <.05) in knockout versus wild-type mice after 4 weeks of aldosterone infusion. Aldosterone infusion increased fibrosis and apoptosis (TUNEL-positive) in both wild-type and knockout mice. However, the increase in the extent of fibrosis and apoptosis was significantly lower in knockout hearts.


CONCLUSIONS
Increased osteopontin plays an important role in the regulation of aldosterone-induced remodeling with effects on left ventricular dilation, fibrosis, and apoptosis.
Sam
Flora
F
Cardiology Section, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
Xie
Zhonglin
Z
Ooi
Henry
H
Kerstetter
David L
DL
Colucci
Wilson S
WS
Singh
Mahipal
M
Singh
Krishna
K
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D001794:Blood Pressure; D004108:Dilatation, Pathologic / Q000000981:diagnostic imaging; D004195:Disease Models, Animal; D004452:Echocardiography; D005355:Fibrosis; D006321:Heart / Q000187:drug effects*; D007150:Immunohistochemistry; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D053495:Osteopontin; D012795:Sialoglycoproteins / Q000378:metabolism*; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology*
D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin; D000450:Aldosterone