Trieu V N, Uckun F M
Department of Cardiovascular Biology and Molecular Epidemiology Program, Wayne Hughes Institute, 2665 Long Lake Road, St. Paul, Minnesota, 55113, USA.
Biochem Biophys Res Commun. 1998 Jun 18;247(2):277-9. doi: 10.1006/bbrc.1998.8776.
Hypertension is more common among African Americans than Americans of European descent. However, the genetic etiology has not been defined. Similarly, lipoprotein (Lp) (a), an independent risk factor for cardiovascular disease, is higher among African Americans. To explore the relationship between Lp (a) and hypertension, we measured the blood pressure of transgenic mice expressing apolipoprotein(a), the unique protein moiety of lipoprotein(a). As controls, we also determined blood pressure for apoE deficient mice, low density lipoprotein-receptor (LDL-R) deficient mice, and wild type C57Bl/6 mice. Apo(a) expression was not associated with hypertension. Surprisingly, LDL-R deficient mice exhibited male-associated hypertension. This observation could explain the higher incidence of atherosclerosis in male LDL-R deficient mice and human familial hypercholesterolemia (FH) patients. LDL-R deficient mice were more sensitive to photochemically induced cerebral stroke. However, this hypersensitivity was only modestly associated with sexual dimorphism. The presented data suggest that LDL-R deficiency results in hitherto unrecognized changes in the vascular tone.
高血压在非裔美国人中比在欧洲裔美国人中更为常见。然而，其遗传病因尚未明确。同样，脂蛋白(a)作为心血管疾病的一个独立危险因素，在非裔美国人中水平更高。为了探究脂蛋白(a)与高血压之间的关系，我们测量了表达载脂蛋白(a)（脂蛋白(a)的独特蛋白质部分）的转基因小鼠的血压。作为对照，我们还测定了载脂蛋白E缺陷小鼠、低密度脂蛋白受体（LDL-R）缺陷小鼠和野生型C57Bl/6小鼠的血压。载脂蛋白(a)的表达与高血压无关。令人惊讶的是，LDL-R缺陷小鼠表现出与雄性相关的高血压。这一观察结果可以解释雄性LDL-R缺陷小鼠和人类家族性高胆固醇血症（FH）患者中动脉粥样硬化发病率较高的现象。LDL-R缺陷小鼠对光化学诱导的脑卒中超敏感。然而，这种超敏感性仅与性别二态性有适度关联。所呈现的数据表明，LDL-R缺陷会导致血管张力出现迄今未被认识到的变化。
