Department of Translational Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, 309 E. Second Street, Pomona, CA, 91766, USA.
Mol Cell Biochem. 2023 Aug;478(8):1887-1898. doi: 10.1007/s11010-022-04643-6. Epub 2022 Dec 28.
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.
高脂血症是肌腱病发生和进展的一个重要危险因素,但它在加重肩袖肌腱损伤(RCTI)中的作用在很大程度上尚不清楚。我们旨在评估肌腱组织和肌腱细胞在高脂血症下关键细胞外基质(ECM)成分的表达状态。从高脂血症猪模型中获取的肩袖 RC 肌腱组织显示出组织形态计量学的改变以及主要 ECM 成分蛋白(包括 COL-I、COL-III、COL-IV、COL-V、COL-VI、MMP2 和 MMP9)的表达状态改变。同样,LDL 和 oxLDL 挑战的肌腱细胞在转录和翻译水平上显示出相同蛋白的改变表达。此外,与对照组相比,脂质挑战的肌腱细胞中脂质摄取和细胞活性氧自由基占优势。总的来说,与 ox-LDL 处理的细胞相比,LDL 处理的细胞显示出主要的病理改变。进一步了解导致肌腱基质改变和随后高脂血症中加重 RCTI 病理的潜在分子机制,可以为 RCTI 的管理开辟新的转化途径。