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Pathological alterations in the expression status of rotator cuff tendon matrix components in hyperlipidemia

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Abstract

Hyperlipidemia is an important risk factor in the development and progression of tendon pathology, however its role in aggravating rotator cuff tendon injury (RCTI) is largely unknown. We aimed to assess the expression status of key extracellular matrix (ECM) components in the tendon tissues and tenocytes under hyperlipidemia. Shoulder rotator cuff (RC) tendon tissues harvested from the swine model of hyperlipidemia displayed alterations in histomorphometry and the expression status of major ECM component proteins including COL-I, COL-III, COL-IV, COL-V, COL-VI, MMP2, and MMP9. Similarly, the LDL- and oxLDL-challenged tenocytes displayed altered expression of the same proteins at both transcriptional and translational levels. In addition, the lipid uptake and cellular reactive oxygen radicals predominated in the lipid-challenged tenocytes compared to the control. Overall, the LDL-treated cells displayed predominant pathological alterations compared to the ox-LDL-treated cells. Further understanding regarding the underlying molecular mechanisms driving the tendon matrisome alteration and subsequent aggravated RCTI pathology in hyperlipidemia could open novel translational avenues in the management of RCTI.

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Data availability

Data with the raw counts matrices and annotation are available upon request from the authors through proper channels.

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Acknowledgements

FGT is thankful to WU for the startup funds and DKA is grateful to National Institutes of Health, USA for funding.

Funding

The research work of FGT is supported by the startup funds from WU and DK Agrawal is supported by research grants R01 HL144125 and R01HL147662 from the National Institutes of Health, USA.

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Authors and Affiliations

  1. Department of Translational Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, 309 E. Second Street, Pomona, CA, 91766, USA

    William Fang, Seerat Sekhon, Darren Teramoto, Cameron Fung, Vy La, Cindy Duong, Christian Doescher, An Thai, Finosh G. Thankam & Devendra K. Agrawal

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  1. William Fang
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Contributions

WF: experimental design; data generation; data analysis; manuscript preparation; preparation of figures; manuscript editing. SS: data generation; data analysis; manuscript editing. DT: data generation; data analysis; manuscript editing. CF: data generation; data analysis; manuscript editing. VL: data generation; data analysis; manuscript editing. CD: data generation; manuscript editing;. CD: data generation; manuscript editing. DKA: Conceptualization; experimental design, manuscript preparation; manuscript editing; resources; funding. FGT: Conceptualization; experimental design, data generation; data analysis; manuscript preparation; manuscript editing; resources; funding.

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Correspondence to Devendra K. Agrawal.

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Fang, W., Sekhon, S., Teramoto, D. et al. Pathological alterations in the expression status of rotator cuff tendon matrix components in hyperlipidemia. Mol Cell Biochem 478, 1887–1898 (2023). https://doi.org/10.1007/s11010-022-04643-6

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