Atomic force microscope studies demonstrate enhanced beta1‐integrin adhesion as a factor assocatiated with age‐related increases in vascular smooth muscle stiffness

Abstract

Beta1-integrin, an important vascular smooth muscle cell-extracelluar matrix (VSMC-ECM) adhesion molecule, shows enhanced VSMC expression associated with age-related increases in aortic stiffness. We investigated whether active beta 1-integrin adhesion to the ECM protein collagen type 1 (COL1) and fibronectin (FN) was enhanced in VSMC from old and young male monkey thoracic aortas using the atomic force microscopic (AFM). As the abundance of beta1-integrin is significantly higher in old compared to young monkeys, we hypothesized that enhanced beta 1-integrin adhesion could provide a mechanism for accentuating aortic stiffness by strengthening VSMC-ECM connections. As evidence of increased beta 1-integrin expression in old vs young VSMC, AFM probes functionalized with FN or COL1 exhibited significantly increased adhesion to the beta1-integrin in old vs young VSMC. In old vs young, COL1 binding probability was 70±1% vs 63±1% and adhesion force was 72±1.3 pN vs 50±2 pN whereas for FN binding probability was 43±1% vs 33±1% and adhesion force 61±1.4 pN vs 39 ± 1 pN. Our results support the involvement of beta1-integrin as a potential factor in the increased stiffness of VSMC observed during aging that could contribute to enhanced stiffness of the aortic wall. (NIH R01HL102472 and P01HL095486).