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Age-associated aortic stenosis in apolipoprotein E-deficient mice
Kimie Tanaka1, Masataka Sata, Daiju Fukuda
1Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Journal of the American College of Cardiology
|July 5, 2005
Summary
Aortic valve sclerosis in aged apolipoprotein E-deficient mice resembles human aortic stenosis. Bone marrow-derived cells contribute to this degeneration, with some differentiating into smooth muscle-like cells.
Area of Science:
- Cardiovascular Research
- Aging Biology
- Pathology
Background:
- Age-associated valvular degeneration involves lipid accumulation, collagen deposition, and calcification.
- The cellular and molecular drivers of age-related valvular changes are not fully understood.
Purpose of the Study:
- To assess aortic valve morphology and function in aged mice.
- To investigate the role of bone-marrow-derived cells in aortic stenosis pathogenesis.
Main Methods:
- Echocardiography and histological analysis of aortic valves in senile wild-type and apolipoprotein E (ApoE)-/- mice.
- Bone marrow transplantation using green fluorescent protein (GFP) or beta-galactosidase (LacZ) reporter mice.
- Immunohistochemistry and electron microscopy to identify cell types and calcification.
Main Results:
- Aortic valve sclerosis in old ApoE-/- mice mimicked human aortic stenosis.
- A significant proportion of bone-marrow-derived cells in sclerotic valves expressed alpha-smooth muscle actin.
- Osteoblast-related proteins were found near ectopic calcifications, and sclerotic valves showed increased apoptosis and chemokine expression.
Conclusions:
- Senile ApoE-deficient mice serve as a model for human aortic valve sclerosis.
- Bone marrow-derived cells, including smooth muscle-like cells, contribute to aortic valve degeneration.
- Apoptotic cell death and chemokine signaling are implicated in the pathogenesis of senile aortic valve sclerosis.