Cor Vasa 2004, 45(2):68-72

Heart transplantation in apolipoprotein E-deficient mice as a model of atherosclerosis regression

Dagmar Bobková^1,*, Jitka Kočová², Zbyněk Tonar², Jiří Lácha³, Jana Havlíčková⁴, Rudolf Poledne¹

¹ Laboratoř pro výzkum aterosklerózy, Institut klinické a experimentální medicíny, Centrum experimentálního výzkumu chorob srdce a cév, Praha

² Oddělení histologie a embryologie, Lékařská fakulta Univerzity Karlovy, Plzeň

³ Nefrologická klinika, Transplantační oddělení

⁴ Laboratoř patofyziologie kardiovaskulárních systému, Institut klinické a experimentální medicíny, Centrum experimentálního výzkumu chorob srdce a cév, Praha, Česká republika

Atherosclerosis is a long-term process of structural changes involving the vessel wall, which are characterized by potential regression. We tested the possibility of using a model of heart transplantation to study atherosclerosis regression in mice with spontaneous development of atherosclerosis, that is, in homozygous apolipoprotein E-deficient mice (apo E KO). Compared with wild-type mice on chow diet (2.3 ± 0.15 mmol/L), apo E KO mice show markedly higher cholesterol levels (10.3 ± 1.40 mmol/L) and the cholesterol/triglyceride ratio in VLDL fraction. After feeding a cholesterol-rich diet, cholesterolemia increased dramatically by a factor of 2.3 in these mice, with pronounced changes in the cholesterol/triglyceride ratio (with wild-type mice showing only a 1.3-fold increase). Before transplantation, the apo E KO mice were fed a cholesterol-rich diet for 4 months in order to develop atherosclerotic lesions. The hearts of apo E KO mice and wild-type mice were transplanted into wild-type mice and evaluated at one month post-transplant. Compared to normal hearts, the heart transplants were smaller and atrophied. In all animals under study, the aortic sinus contained atherosclerotic plaques. In the transplant apo E KO and wild-type mice, the plaques were mostly athrombogenic, containing collagen fibers and smooth muscle cells. Compared to transplant animals, the atherosclerotic plaques of apo E KO mice without transplantation were found to be more vulnerable. It was concluded heart transplantation in experimental model of mice is not a suitable model for studying atherosclerosis regression.

Keywords: Apolipoprotein E-deficient mice; Atherosclerosis; Heart transplantation; Regression

Published: February 1, 2004  Show citation