Abstract
It is unclear how microangiopathic changes in skeletal muscle vary among systemic vascular pathologies. We therefore analyzed the capillary fine structure in skeletal muscle from patients with arterial hypertension (HYPT), diabetes mellitus type 2 (T2DM) or intermittent claudication – peripheral arterial disease (IC/PAD). Tablet-based image analysis (TBIA) was carried out to largely re-evaluate 5,000 transmission electron micrographs of capillaries from 126 vastus lateralis biopsies of 75 individuals (HYPT, T2DM or IC/PAD patients as well as healthy individuals before and after endurance exercise training) used in previous morphometric studies, but assessed using stereological counting grids of different sizes. Serial block-face scanning electron microscopy (SBFSEM) of mouse skeletal muscle was used for validation of the particular fine structural events observed in human biopsies. The peri-capillary basement membrane (BM) was 38.5 and 45.5% thicker (P < 0.05) in T2DM and IC/PAD patients than in the other groups. A 17.7–39.6% lower (P < 0.05) index for intraluminal endothelial cell (EC) surface enlargement by projections was exclusively found in T2DM patients by TBIA morphometry. The proportion of capillaries with disrupted BM between pericytes (PC) and EC was higher (P < 0.05) in HYPT (33.2%) and T2DM (38.7%) patients than in the control group. Empty EC-sockets were more frequent (P < 0.05) in the three patient groups (20.6% in HYPT, 27.1% in T2DM, 30.0% in IC/PAD) than in the healthy individuals. SBFSEM confirmed that EC-sockets may exhibit close proximity to the capillary lumen. Our comparative morphometric analysis demonstrated that structural arrangement of skeletal muscle capillaries is more affected in T2DM than in HYPT or IC/PAD, although some similar elements of remodeling were found. The increased frequency of empty EC-sockets in the three patient groups indicates that the PC-EC interaction is commonly disturbed in these systemic vascular pathologies.
Highlights
Capillaries are the major sites of diffusive oxygen exchange and removal of catabolic products in all tissue, and represent a crucial structural element defining functional capacity of the cardiovascular system
The transmission electron microscope (TEM) micrographs always showed an evident lumen enclosed by a continuous endothelial cell (EC) layer, and a basement membrane (BM) present at the abluminal surface in which a variable number of pericyte (PC) profiles were embedded
We were interested in differences in capillary phenotype of HYPT, type-2 diabetes mellitus (T2DM) and intermittent claudication – peripheral arterial disease (IC/peripheral arterial disease (PAD)) patients compared to healthy individuals, which may identify structural microangiopathies specific for these systemic vascular pathologies
Summary
Capillaries are the major sites of diffusive oxygen exchange and removal of catabolic products in all tissue, and represent a crucial structural element defining functional capacity of the cardiovascular system. A transient hyperfiltration through the glomerular capillary loops is established, which together with glomerular hypertony and hyperperfusion (due to constriction of efferent arterioles) progresses to clinically manifested micro- and macroalbuminuria, and kidney necrosis (Kanwar et al, 2011; Vallon and Komers, 2011). The vessel walls become leaky due to endothelial cell (EC) apoptosis, inducing capillaries to undergo rarefaction (Kur et al, 2012). These processes combine to establish retinal ischemia, which elicits VEGF-mediated angiogenesis as a compensatory response, and excessive capillary proliferation leads to visual disturbances or blindness (Kur et al, 2012). The turnover of PC is accelerated (Tilton et al, 1981), and EC apoptosis rates are increased (Vracko and Benditt, 1970)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
