Oguchi A, Ikeda U, Miyashita H, Ohara T, Tsuruya Y, Natsume T, Yaginuma T, Shimada K
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Atherosclerosis. 1991 Oct;90(2-3):101-8. doi: 10.1016/0021-9150(91)90104-b.
The Watanabe Heritable Hyperlipidemic (WHHL) rabbit is a widely studied animal model for the human genetic disorder familial hypercholesterolemia, and spontaneously develops atherosclerotic disease. We studied the growth characteristics of cultured vascular smooth muscle cells (VSMC) from WHHL rabbits compared with VSMC from Japanese white rabbits. We measured cell proliferation, DNA synthesis, and c-myc proto-oncogene expression, in response to growth stimuli such as fetal bovine serum (FBS) and platelet-derived growth factor (PDGF). VSMC from Japanese white rabbits exhibited a 4-fold increase in cell numbers during a 5-day incubation period compared with those from WHHL rabbits. FBS and PDGF stimulated DNA synthesis, as measured by thymidine incorporation into VSMC, in both Japanese white rabbits and WHHL rabbits, however the response was significantly higher in the former strain. The intracellular pH value of VSMC determined using the pH-sensitive fluorescence dye 2',7'-bis-carboxyethyl-carboxyfluorescein was significantly higher in WHHL rabbits than in Japanese white rabbits. Proto-oncogene c-myc was induced by exposure of VSMC to FBS, however there was no significant difference in c-myc mRNA levels between the two strains. These results suggest that VSMC from WHHL rabbits are not genetically growth accelerated, but show decreased growth response to growth stimuli.
渡边遗传性高脂血症（WHHL）兔是一种广泛用于研究人类遗传性疾病家族性高胆固醇血症的动物模型，它会自发发展为动脉粥样硬化疾病。我们研究了WHHL兔培养的血管平滑肌细胞（VSMC）与日本白兔VSMC的生长特性。我们测量了细胞增殖、DNA合成以及c-myc原癌基因表达，以响应诸如胎牛血清（FBS）和血小板衍生生长因子（PDGF）等生长刺激。与WHHL兔的VSMC相比，日本白兔的VSMC在5天的孵育期内细胞数量增加了4倍。FBS和PDGF刺激了DNA合成，通过胸苷掺入VSMC来测量，在日本白兔和WHHL兔中均如此，然而前一种品系的反应明显更高。使用pH敏感荧光染料2',7'-双羧乙基羧基荧光素测定的WHHL兔VSMC的细胞内pH值显著高于日本白兔。原癌基因c-myc是由VSMC暴露于FBS诱导的，然而两种品系之间c-myc mRNA水平没有显著差异。这些结果表明，WHHL兔的VSMC在遗传上并非生长加速，而是对生长刺激的生长反应降低。
