The impact of mild hypercholesterolemia on injury repair in the rat patellar tendon

Abstract

AbstractHypercholesterolemia 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.