Schwenke D C, Carew T E
Specialized Center of Research on Atherosclerosis, University of California, San Diego, La Jolla 92093.
Circ Res. 1988 Apr;62(4):699-710. doi: 10.1161/01.res.62.4.699.
While the exact mechanisms that initiate atherosclerotic lesions are unknown, considerable evidence supports a role for low density lipoprotein (LDL). We investigated whether in the normal rabbit, LDL metabolism in areas of aorta that are destined to become lesioned during cholesterol feeding differed from the metabolism in adjacent lesion-resistant aorta. These studies took advantage of the predictable pattern of early atherosclerotic lesions in the cholesterol-fed rabbit. Early lesions occur diffusely in the aortic arch and ascending aorta and distal to branch orifices in the abdominal aorta and the descending thoracic aorta. Arterial rates of irreversible degradation of LDL and concentrations of intact LDL were measured in susceptible and resistant sites with homologous doubly labeled LDL. LDL was labeled directly with 131I and with 125I-tyramine cellobiose. The latter label provides a highly sensitive means to determine the sites and rates of lipoprotein degradation in vivo. The arterial concentration of intact LDL in the lesion-prone aortic arch was 3.12 +/- 0.45 micrograms LDL cholesterol/g (n = 14), 3.6 +/- 0.69 times that in the relatively lesion-resistant descending thoracic aorta (p less than 0.001). The rate of LDL degradation in the aortic arch was 3.14 +/- 0.41 micrograms LDL cholesterol/g/day, 2.14 +/- 0.24 times that in the descending thoracic aorta (p less than 0.001). In the abdominal aorta, the LDL (per gram wet weight) concentration and degradation rate (per square centimeter surface area) at branch sites exceeded that at nonbranch sites by 88 +/- 11% (p less than 0.001) and by 61 +/- 8% (p less than 0.001), respectively. These data provide evidence that in the normal rabbit, which does not develop atherosclerotic lesions, focal elevations of arterial LDL degradation rate and concentrations of intact LDL occur at sites that first develop atherosclerotic lesions in the hypercholesterolemic animal. These differences in LDL metabolism may be linked causally to the propensity to develop atherosclerotic lesions at these sites.
虽然引发动脉粥样硬化病变的确切机制尚不清楚，但大量证据支持低密度脂蛋白（LDL）发挥了作用。我们研究了在正常兔体内，在胆固醇喂养期间注定会发生病变的主动脉区域的LDL代谢，是否与相邻的抗病变主动脉中的代谢不同。这些研究利用了胆固醇喂养兔早期动脉粥样硬化病变的可预测模式。早期病变广泛发生在主动脉弓和升主动脉，以及腹主动脉和胸降主动脉分支孔远端。使用同源双标记LDL测量易感部位和抗病变部位的LDL不可逆降解动脉速率和完整LDL浓度。LDL直接用131I和125I - 纤维二糖酪胺标记。后一种标记提供了一种在体内确定脂蛋白降解部位和速率的高度灵敏方法。易发生病变的主动脉弓中完整LDL的动脉浓度为3.12±0.45微克LDL胆固醇/克（n = 14），是相对抗病变的胸降主动脉中浓度的3.6±0.69倍（p < 0.001）。主动脉弓中LDL降解速率为3.14±0.41微克LDL胆固醇/克/天，是胸降主动脉中降解速率的2.14±0.24倍（p < 0.001）。在腹主动脉中，分支部位的LDL（每克湿重）浓度和降解速率（每平方厘米表面积）分别比非分支部位高88±11%（p < 0.001）和61±8%（p < 0.001）。这些数据表明，在未发生动脉粥样硬化病变的正常兔中，在高胆固醇血症动物中首先发生动脉粥样硬化病变的部位，动脉LDL降解速率和完整LDL浓度会出现局部升高。这些LDL代谢差异可能与这些部位发生动脉粥样硬化病变的倾向存在因果联系。
