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Changes in arterial function in a mouse model of human familial hypercholesterolaemia
O Brinkmann1, K Schmerbach, U J F Tietge
1Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Insights
Atherosclerosis impairs blood vessel function, with reduced dilation seen in older ApoB mice. Young ApoB mice show early vascular changes, indicating altered vessel reactivity before severe atherosclerosis develops.
Area of Science:
- Cardiovascular Research
- Vascular Biology
- Animal Models
Background:
- Atherosclerosis is a leading cause of cardiovascular disease.
- The ApoB mouse model mimics human familial hypercholesterolaemia and atherosclerosis.
- Understanding vascular changes during atherogenesis is crucial.
Purpose of the Study:
- To investigate arterial contractile and dilatative properties in ApoB mice.
- To assess age-related changes in vasoreactivity during atherogenesis.
- To correlate vascular function with atherosclerosis development.
Main Methods:
- Isometric myography of thoracic aorta ring preparations.
- Assessment of male ApoB and wild-type (WT) mice at 4 and 18 months.
- Histological, biochemical analysis for atherosclerosis, lipids, and endothelial markers.
Main Results:
- Old ApoB mice exhibited severe aortic atherosclerosis and diminished acetylcholine-induced vasodilation.
- Young ApoB mice showed significantly attenuated phenylephrine response, indicating early vascular dysfunction.
- Elevated total cholesterol, triglycerides, sICAM-1, and sVCAM-1 were observed in ApoB mice.
Conclusions:
- Reduced acetylcholine-induced vasodilation is linked to atherosclerosis in aged ApoB mice.
- Early impairment in vascular reactivity to phenylephrine in young ApoB mice suggests preclinical changes.
- The ApoB mouse model is valuable for studying age-related vascular dysfunction in atherosclerosis.
Aim:
Atherosclerosis is the most common cause of cardiovascular disease. The ApoB mouse is a model for human familial hypercholesterolaemia and has a lipoprotein profile similar to that of humans with atherosclerosis. Therefore, it is a suitable model to investigate the changes in vasoreactivity during atherogenesis. This study investigates contractile and dilatative properties of arteries in this model in relation to age.
Methods:
Male ApoB mice and B6, wild-type (WT), mice were examined at age four or 18 months. Isometric measurements of 2-mm ring preparations of the aorta thoracica were performed using a wire myograph. Histological and biochemical methods served to determine atherosclerosis, lipid status and endothelial markers respectively.
Results:
Morphometric analysis showed that all old ApoB mice had severe atherosclerosis in the aorta. Atherosclerotic alteration of the aorta of the ApoB mice coincided with a diminished vasodilatation to acetylcholine. The phenylephrine response was significantly attenuated already to the same degree in the non-atherosclerotic aorta of the young ApoB mice as in the atherosclerotic aorta of the older ApoB mice. Serum parameters showed a rise in total cholesterol and triglycerides in the ApoB strain compared to WT mice. Soluble intercellular adhesion molecule (sICAM)-1 and soluble vascular adhesion molecule (sVCAM)-1 were increased in old compared to young ApoB mice.
Conclusion:
The study shows that reduced acetylcholine-induced dilatation is related to the presence of atherosclerosis in old ApoB mice. Remarkably, the impaired vessel reactivity to phenylephrine already in young ApoB mice indicates early changes in vascular function in this model.
