Abstract Th0066: Role of Vascular Smooth Muscle Cell Mechanics in Vascular Wall Stiffening

Vascular stiffening is one of the most prevalent age-associated cardiovascular events. Controlling arterial stiffness has been proposed as a novel strategy for the pharmacological treatment of these conditions in aging populations. Despite significant therapeutic advancements over the past several decades, arterial stiffening and its associated cardiovascular diseases (CVDs) remain major health challenges in aging societies. Previous studies on arterial stiffness have predominantly focused on endothelial or extracellular matrix (ECM)-related mechanisms. However, the direct contribution of the mechanical properties of vascular smooth muscle cells (VSMCs) to arterial stiffness is not well understood. Verteporfin (VP), a porphyrinic photosensitizer, is clinically utilized in photodynamic therapy to treat age-related macular degeneration. To our knowledge, its impact on vascular cell mechanics, particularly VSMC mechanics, has been largely unexplored. In this study, we investigated the potential of VP therapy to mitigate age-related vascular stiffening and prevent the development of associated CVDs. An atomic force microscope (AFM) was employed to assess VSMC adhesion, stiffness, and submembranous cytoskeletal organization. Data-driven, mathematical model-based image and signal processing software was used to analyze the AFM data. Statistical significance for all experiments was determined using two-way ANOVA. Our results demonstrated that VP treatment significantly disrupted actin cytoskeletal organization and reduced VSMC stiffness compared to control cells. Interestingly, VP also regulated cell adhesion in an ECM-dependent manner. These findings reveal a novel role for VP in modulating VSMC mechanics and provide new insights into the mechanisms underlying arterial stiffening with aging. Furthermore, this study highlights the potential of VP as a therapeutic strategy for treating CVDs related to vascular stiffening.