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Review
. 2023 May;392(2):431-442.
doi: 10.1007/s00441-023-03748-8. Epub 2023 Feb 4.

Hyperlipidemia in tendon injury: chronicles of low-density lipoproteins

William H Fang  1 , Victor Bonavida  1 , Devendra K Agrawal  1 , Finosh G Thankam  2
Affiliations
Review

Hyperlipidemia in tendon injury: chronicles of low-density lipoproteins

William H Fang et al. Cell Tissue Res. 2023 May.

Abstract

Hyperlipidemia impacts millions of people globally and has been the major risk factor for developing atherosclerosis and cardiovascular disease. Interestingly, hyperlipidemic subjects exhibit increased incidence of rotator cuff tendon injury (RCTI) and disorganization of tendon matrix. Low-density lipoproteins (LDL) and its oxidized form (ox-LDL) play a crucial role in hyperlipidemia-driven pro-inflammatory responses in multiple tissues including the tendon. The signaling of oxLDL upregulates the inflammatory cytokines, chemokines, adhesion molecules, and the activation of monocytes/macrophages/resident tendon cells and matrix metalloproteinases impairing the tendon homeostasis resulting in the alteration of extracellular matrix. In addition, the hyperlipidemia-driven immune response and subsequent oxidative stress promote degenerative responses in the tendon tissue. However, the pathological mechanisms underlying the occurrence of RCTI in hyperlipidemia and the effect of ox-LDL in tendon matrix are currently unknown. The present review focuses on the implications and perspectives of LDL/oxLDL on the increased incidence of RCTI.

Keywords: ECM disorganization; Hyperlipidemia; LDL; Rotator cuff tendon injury; oxLDL.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
LDL molecular formation pathway from precursor lipid species. The molecular events involve binding of LDL particle on the plasma membrane, followed by internalization, and routing to the lysosome for degradation into fatty acids. However, an overabundance of LDL leads to atherogenesis through the formation of foam cells, lipid-laden macrophages, that localize on blood vessel walls
Fig. 2
Fig. 2
(Left panel) Oxidative molecules and free radicals lead to OxLDL formation. OxLDL increases inflammatory cytokines and polarizes macrophages to M2 phenotype. (Right panel) Downstream signaling of OxLDL and M2 leading to collagen disruption and angiogenesis
Fig. 3
Fig. 3
The intracellular macrophage activation leading to the increased production of proinflammatory cytokines and ROS. Cholesterol reacts with ROS to activate AKT/FOXO1 signaling leading to the histological alterations including degenerative damage in the tendon
See this image and copyright information in PMC

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