McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, PA 19104, USA.
J Shoulder Elbow Surg. 2013 May;22(5):681-6. doi: 10.1016/j.jse.2012.07.008. Epub 2012 Sep 13.
More than one-quarter of Americans have hypercholesterolemia and/or are being treated with cholesterol-lowering medications. Given the systemic nature of hypercholesterolemia and remaining questions regarding its effect on tendons at a local level, we sought to assess the utility of small versus large animal model systems for translational studies by exploring the effect of hypercholesterolemia on supraspinatus tendon elastic mechanical properties in mice, rats, and monkeys. We hypothesized that stiffness and elastic modulus would be increased in tendons across species due to hypercholesterolemia.
Supraspinatus tendons from normal (control) and high-cholesterol (HC) mice, rats, and monkeys were used in this study. After dissection, tendons were geometrically measured and tensile tested with tissue strain measured optically.
Overall, HC animals had significantly altered plasma lipid profiles. Biomechanical testing showed a significant increase in stiffness compared with control in HC mice and rats, as well as a nonsignificant trend for HC monkeys. Elastic modulus was also significantly increased in HC mice and monkeys, with HC rats showing a trend.
The consistency of our findings across species and between small and large animals, combined with the fact that the aged mice were exposed to lifelong hypercholesterolemia (compared with rats and nonhuman primates, which were fed HC diets), suggests that these increased properties may be inherent to the effect of hypercholesterolemia on supraspinatus tendon rather than due to an effect of cumulative exposure time to the effects of HC. Further investigation is needed to confirm this concept.
超过四分之一的美国人患有高胆固醇血症,或正在服用降胆固醇药物。鉴于高胆固醇血症的系统性以及其对局部肌腱的影响仍存在疑问,我们试图通过探索高胆固醇血症对小鼠、大鼠和猴子的冈上肌腱弹性力学特性的影响,评估小动物和大动物模型系统在转化研究中的应用。我们假设由于高胆固醇血症,跨物种的肌腱刚度和弹性模量会增加。
本研究使用了正常(对照)和高胆固醇(HC)小鼠、大鼠和猴子的冈上肌腱。解剖后,通过光学测量组织应变对肌腱进行几何测量和拉伸测试。
总体而言,HC 动物的血浆脂质谱发生了明显改变。生物力学测试显示,与对照组相比,HC 小鼠和大鼠的肌腱刚度显著增加,而 HC 猴子则呈现出非显著趋势。HC 小鼠和猴子的弹性模量也显著增加,而 HC 大鼠则呈现出增加的趋势。
我们的研究结果在不同物种和大小动物之间具有一致性,并且年老的小鼠暴露于终生高胆固醇血症(与大鼠和非人类灵长类动物相比,它们只接受了高胆固醇饮食),这表明这些增加的特性可能是高胆固醇血症对冈上肌腱的固有影响,而不是由于累积暴露时间对高胆固醇血症的影响所致。需要进一步研究来证实这一概念。