Changes in arterial function in a mouse model of human familial hypercholesterolaemia

Autor: U. J. F. Tietge, H. Guski, Hans-Georg Kuhn, Kristin Schmerbach, Andreas Patzak, T. Dietrich, Dominik Linz, O. Brinkmann, K. Wilfert
Přispěvatelé: Center for Liver, Digestive and Metabolic Diseases (CLDM), Lifestyle Medicine (LM)
Rok vydání: 2014
Předmět:
Male
Apolipoprotein E
medicine.medical_specialty
Apolipoprotein B
HERITABLE HYPERLIPIDEMIC RABBITS
RECEPTOR KNOCKOUT MICE
Physiology
Vascular Cell Adhesion Molecule-1
Aorta
Thoracic
vessel function
Vasodilation
CELL-ADHESION MOLECULE-1
endothelial dysfunction
ENDOTHELIUM-DEPENDENT RELAXATION
APOLIPOPROTEIN-E
Hyperlipoproteinemia Type II
Mice
ATHEROSCLEROTIC LESIONS
Internal medicine
medicine.artery
medicine
Animals
CHOLESTEROL-FED RABBITS
Endothelial dysfunction
Phenylephrine
Apolipoproteins B
E-DEFICIENT MICE
Aorta
NITRIC-OXIDE
biology
business.industry
COMMON CAROTID ARTERIES
nutritional and metabolic diseases
Arteries
Intercellular Adhesion Molecule-1
medicine.disease
Intercellular adhesion molecule
Disease Models
Animal
aorta
Cholesterol
Endocrinology
biology.protein
lipids (amino acids
peptides
and proteins)
atherosclerosis
business
medicine.drug
Myograph
Zdroj: Acta physiologica, 211(1), 61-72. Wiley
ISSN: 1748-1708
Popis: AimAtherosclerosis 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.MethodsMale ApoB mice and B6, wild-type (WT), mice were examined at age four or 18months. 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.ResultsMorphometric 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.ConclusionThe 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.
Databáze: OpenAIRE
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