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The link between hypercholesterolemia and tendon pathology Grewal, Navdeep


Tendinopathy is a major cause of morbidity in athletic populations and in the work force, traditionally thought to occur as a consequence of an imbalance between damage (resulting from mechanical loading) and repair. However, one third of the cases for midportion Achilles tendinopathy occur in sedentary individuals, and recent data suggests an association between hypercholesterolemia and the occurrence of tendon rupture or tendinopathy. The aim of this study was to examine the link between elevated lipids and tendon pathology. We used an apolipoprotein E-knockout model (ApoE-KO), in which apolipoprotein E deficiency leads to development of atherosclerosis. We hypothesized that tendons from ApoE-KO mice fed a high fat diet, in comparison to those fed a regular chow diet and the wild type (non-atherosclerotic mice), will demonstrate increased lipid deposition, increased cross-sectional area, and increased expression levels of collagen genes (Col1a1 and Col3a1), a growth factor gene (TGF-β), and an indicator of mast cell presence (Cpa3). To test these hypotheses, ApoE-KO and control mice were fed a regular or high fat diet and sacrificed at different time points: 0, 15, and 30 weeks. The morphological properties were examined on H&E stained Achilles tendon sections while the lipid content was analyzed with Oil Red O staining. Tendon thickening was measured by ultrasonography of patellar tendon cross-sectional area. qPCR analysis was carried out on tail tendons at 30 week time point to analyze gene expression of Cpa3, TGF-β, Col1a1, and Col3a1. ApoE-KO mice developed xanthomatous lesions, and showed less weight gain than control mice. ApoE-KO mice showed no appreciable changes in tendon histomorphology. Compared to control mice, ApoE-KO mice had lower tendon lipid content but demonstrated an increase in tendon cross-sectional area. Col1a1 gene expression levels were decreased in ApoE-KO mice. Cpa3, TGF-β, and Col3a1 showed no differences between strains; however, Cpa3 expression was decreased in mice that were fed the high fat diet. ApoE-KO mice demonstrated significant tendon alterations, demonstrating thicker tendons with decreased collagen expression. Future work is required to determine the mechanism involved and the potential impact on tendon function.

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