Microstructural Characterization 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.

Intermittent compression induces transitory hypoxic stimuli, upstream vasodilation and enhanced perfusion of skin capillaries, independent of age and diabetes.

The benefit of enhanced shear stress to the vascular endothelium has been well-documented in conduit arteries but is less understood in skin microcirculation. The aim of this study was to provide physiological evidence of the vascular changes in skin microcirculation induced by intermittent pneumatic compression (IPC) of 1 s cuff inflation (130 mmHg) every 20 s to the palm of the hand for 30 min. The oxygenation and hemodynamics of dorsal mid-phalangeal finger skin microcirculation were assessed by laser Doppler fluximetry and reflectance spectroscopy before, during, and after IPC in 15 young (18-39 years old) and 39 older (40-80 years old) controls and 32 older subjects with type 2 diabetes mellitus. Each individual cuff inflation induced: 1) brief surge in flux immediately after cuff deflation followed by 2) transitory reduction in blood oxygen for ∼4 s, and 3) a second increase in perfusion and oxygenation of the microcirculation peaking ∼11 s after cuff deflation in all subject groups. With no significant change in blood volume observed by reflectance spectroscopy, despite the increased shear stress at the observed site, this second peak in flux and blood oxygen suggests a delayed vasoactive response upstream inducing increased arterial influx in the microcirculation that was higher in older controls and subjects with diabetes compared to young controls (P < 0.001, P < 0.001, respectively) and achieving maximum capillary recruitment in all subject groups. Transitory hypoxic stimuli with conducted vasodilation may be a mechanism through which IPC enhances capillary perfusion in skin microcirculation independent of age and type 2 diabetes mellitus.NEW & NOTEWORTHY This study demonstrates that hand intermittent pneumatic compression evokes transitory hypoxic stimuli in distal finger skin microcirculation inducing vasodilation of arterial inflow vessels, enhanced perfusion, and maximum capillary recruitment in young and older subjects and older subjects with type 2 diabetes mellitus. Enhanced shear stress in the microcirculation did not appear to induce local skin vasodilation.