Microstructure and mechanics of human resistance arteries.

Abstract

Vascular diseases such as diabetes and hypertension cause changes to the vasculature that can lead to vessel stiffening and the loss of vasoactivity. The microstructural bases of these changes are not presently fully understood. We present a new methodology for stain-free visualisation, at a microscopic scale, of the morphology of the main passive components of the walls of unfixed resistance arteries and their response to changes in transmural pressure. Human resistance arteries were dissected from subcutaneous fat biopsies, mounted on a perfusion myograph and imaged at varying transmural pressures using a multimodal nonlinear microscope. High resolution 3D images of elastic fibres, collagen and cell nuclei were constructed. The honeycomb structure of the elastic fibers comprising the internal elastic layer became visible at a transmural pressure of 30 mmHg. The adventitia, comprising wavy collagen fibres punctuated by straight elastic fibres, thinned under pressure as the collagen network straightened and pulled taut. Quantitative measurements of fibre orientation were made as a function of pressure. A multi-layer analytical model was used to calculate the stiffness and stress in each layer. The adventitia was calculated to be up to ten times as stiff as the media and experienced up to 8 times the stress, depending on lumen diameter. This work reveals that pressure-induced reorganisation of fibrous proteins gives rise to very high local strain fields, and highlights the unique mechanical roles of both fibrous networks. It thereby provides a basis for understanding the micromechanical significance of structural changes which occur with age and disease.