4.1 PROBING ARTERIAL STIFFNESS AT THE NANO-SCALE USING THE INTERNAL MAMMARY ARTERY AS A NOVEL TARGET

Abstract

Introduction: Arterial stiffening is associated with structural and biomechanical alterations in the aorta. However, there are still gaps in our understanding as to how the structure and properties of arteries across the vasculature are altered with high PWV.Objective: To determine whether altered ultrastructural and nanomechanical properties are exhibited in the internal mammary artery (IMA) in high PWV patients. Methods: Human IMA biopsies were obtained from patients with known carotid-femoral PWV. Patients were grouped as low PWV (8.5 ± 0.7 ms−1, n = 8) and high PWV (13.4 ± 3.0 ms−1, n = 9). With Peakforce QNM atomic force microscopy (AFM) the nanomechanical (elastic modulus) and morphological properties (collagen fibril diameter and D-Period) of the IMA were measured. Principal component analysis (PCA) was used to determine the relationship of nanomechanical and structural data with proteomics data (small leucine rich proteoglycans, SLRPs) [1] and patient metadata. Results: PCA analysis shows that the nano-scale elastic modulus was one of the key variables which separated low and high PWV groups and was correlated with PWV. Furthermore, nano-scale alterations in adventitial collagen fibrils were evident. D-Period and collagen fibril diameter were found to be negatively correlated. Most SLRPs were closely grouped in the PCA analysis. Conclusions: Although the IMA is not involved in the carotid-femoral pathway, patients with high PWV exhibited distinct alterations in the IMA at the nano-scale relative to those with low PWV. Our approach provides new insight into systemic structure-property changes in the vasculature, and also provides a novel method for characterizing small biopsy samples for arterial stiffening studies.