Microstructural characterisation of resistance artery remodelling in diabetes mellitus

Introduction: Microvascular remodelling is a symptom of cardiovascular disease. Despite the mechanical environment being recognized as a major contributor to the remodelling process, it is currently only understood in a rudimentary way. Objective: A morphological and mechanical evaluation of the resistance vasculature in health and diabetes mellitus. Methods: The cells and extracellular matrix of human subcutaneous resistance arteries from abdominal fat biopsies were imaged using two-photon fluorescence and second harmonic generation at varying transmural pressure. The results informed a two-layer mechanical model. Results: Diabetic resistance arteries reduced in wall area as pressure was increased. This was attributed to the presence of thick, straight collagen fibre bundles that braced the outer wall. The abnormal mechanical environment caused the internal elastic lamina and endothelial and vascular smooth muscle cell arrangements to twist. Conclusions: Our results suggest diabetic microvascular remodelling is likely to be stress-driven, comprising at least 2 stages: (1) Laying down of adventitial bracing fibres that limit outward distension, and (2) Deposition of additional collagen in the media, likely due to the significantly altered mechanical environment. This work represents a step towards elucidating the local stress environment of cells, which is crucial to build accurate models of mechanotransduction in disease