An Angiotensin II Receptor Blocker Suppresses Glucose-Induced Oxidative Stress in Human Rotator Cuff-Derived Cells.

Abstract

Rotator cuff tears are among the most common shoulder disorders, and their incidence increases with age. Hyperglycemic conditions are known to enhance oxidative stress and inflammatory signaling in various tissues, potentially contributing to tendon degeneration. Angiotensin II receptor blockers (ARBs) are widely used antihypertensive agents known to possess antioxidant and anti-inflammatory properties. However, their effects on hyperglycemia-induced oxidative stress in tendon tissues remain unclear. This study investigated whether losartan, an ARB, suppresses high glucose-induced oxidative stress in human rotator cuff-derived cells. Tendon-derived cells obtained during arthroscopic rotator cuff repair were cultured and divided into four groups: control (C), control with losartan (CL; 100 μM), high glucose (H; 33 mM), and high glucose with losartan (HL). Cell viability was evaluated using the Cell Counting Kit-8. Expression of RAGE, NOX1, NOX4, IL-6, IL-1β, COL1, and COL3 was analyzed by quantitative real-time PCR. Reactive oxygen species (ROS) were detected by DCFH-DA staining, and apoptosis was assessed by TUNEL staining. High glucose exposure significantly reduced cell viability and increased ROS production and inflammatory gene expression. Losartan treatment under high-glucose conditions mitigated these changes, maintaining cell viability and suppressing the expression of RAGE, NOX1, IL-6, and IL-1β. These findings suggest that losartan modulates oxidative stress pathways under hyperglycemic conditions and may represent a potential therapeutic strategy.