Department of Physical Therapy, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
School of Engineering and Materials Science, Queen Mary, University of London, London, UK.
J Orthop Res. 2023 Sep;41(9):1871-1881. doi: 10.1002/jor.25546. Epub 2023 Mar 20.
Hypercholesterolemia is associated with tendon pathology and injury prevalence. Lipids can accumulate in the tendon's extracellular spaces, which may disrupt its hierarchical structure and the tenocytes physicochemical environment. We hypothesized that the tendon's ability to repair after injury would be attenuated with elevated cholesterol levels, leading to inferior mechanical properties. Fifty wild-type (sSD) and 50 apolipoprotein E knock-out rats (ApoE ) were given a unilateral patellar tendon (PT) injury at 12 weeks old; the uninjured limb served as a control. Animals were euthanized at 3-, 14,- or 42-days postinjury and PT healing was investigated. ApoE serum cholesterol was double that of SD rats (mean: 2.12 vs. 0.99 mg/mL, p < 0.001) and cholesterol level was related to the expression of several genes after injury; notably rats with higher cholesterol demonstrated a blunted inflammatory response. There was little physical evidence of tendon lipid content or differences in injury repair between groups, therefore we were not surprised that tendon mechanical or material properties did not differ between strains. The young age and the mild phenotype of our ApoE rats might explain these findings. Hydroxyproline content was positively related to total blood cholesterol, but this result did not translate to observable biomechanical differences, perhaps due to the narrow range of cholesterol levels observed. Tendon inflammatory and healing activity is modulated at the mRNA level even with a mild hypercholesterolemia. These important initial impacts need to be investigated as they may contribute to the known consequences of cholesterol on tendons in humans.
高胆固醇血症与肌腱病变和损伤的发生率有关。脂质可以在肌腱的细胞外空间中积累，这可能会破坏其分层结构和肌腱细胞的理化环境。我们假设，随着胆固醇水平的升高，肌腱在受伤后的修复能力会减弱，导致机械性能下降。50 只野生型（sSD）和 50 只载脂蛋白 E 敲除大鼠（ApoE ）在 12 周龄时接受单侧髌腱（PT）损伤；未受伤的肢体作为对照。动物在受伤后 3、14 或 42 天被安乐死，并研究 PT 愈合情况。ApoE 血清胆固醇是 sSD 大鼠的两倍（平均值：2.12 与 0.99 mg/mL，p < 0.001），胆固醇水平与受伤后几个基因的表达有关；值得注意的是，胆固醇水平较高的大鼠表现出炎症反应减弱。各组之间肌腱脂质含量或损伤修复差异几乎没有明显的物理证据，因此我们并不惊讶两组之间的肌腱力学或材料特性没有差异。我们的 ApoE 大鼠年龄较小，表型较轻，这可能解释了这些发现。羟脯氨酸含量与总胆固醇呈正相关，但这一结果并没有转化为可观察到的生物力学差异，可能是由于观察到的胆固醇水平范围较窄。即使存在轻度高胆固醇血症，肌腱的炎症和愈合活性也会在 mRNA 水平上受到调节。这些重要的初步影响需要进一步研究，因为它们可能导致胆固醇对人类肌腱的已知影响。
