Capillary changes in skeletal muscle of patients with Ullrich's disease with collagen VI deficiency

Abstract

We examined the capillaries in muscle biopsy specimens from two patients with Ullrich's disease with collagen VI deficiency by light and electron microscopy. Collagen VI plays an important role in platelet aggregation for binding von Willebrand factor. Using immunohistochemistry, collagen VI was shown to be absent on capillaries from patients with Ullrich's disease, while von Willebrand factor, collagen IV, and vascular endothelial growth factor were normally expressed. Electron microscopy revealed narrow lumens, large nuclei in endothelial cells, and fenestration of a capillary. The number of pinocytotic vesicles per unit endothelial cytoplasm was increased. The cytoplasm of endothelial cells was strongly stained with uranyl acetate and lead citrate. Replication of the capillary basement membrane was observed. On the other hand, easy bleeding and coagulation were not observed in the two patients. These findings suggested that the collagen VI deficiency might have caused the electron microscopic changes of capillaries, while the function of the capillaries is apparently retained.

Autosomal recessive myosclerosis myopathy is a collagen VI disorder

“…Thickening of capillary basement membrane was reported in UCMD patients with complete lack of collagen VI, whereas alterations of pericytes were never reported in UCMD. 33 Capillary basement membrane thickening was observed in Duchenne muscular dystrophy 34 and inflammatory myopathies, 35 being considered an aspect of vascular regeneration occurring during microcirculation remodelling. 34 Unlike in our patients, in those conditions pericytes appeared relatively unaffected.…”

Collagen VI related muscle disorders

“…The basal lamina appeared intact in itself, even in degenerating muscle fibres, with disorganised myofibrils, indicating a loose connection between the basal lamina and other extracellular matrix collagens. 135 Capillaries in muscle biopsy specimens from UCMD patients have been described as being devoid of collagen VI, with associated capillary fenestration on electronmicroscopy 136 ; however, in skin biopsies of UCMD patients the papillary dermis and the hair follicles show a reduced amount of collagen VI protein while vessels, peripheral nerves, smooth muscle, and sweat glands show labelling comparable with normal controls. 11…”

Effects of Topical Icing on Inflammation, Angiogenesis, Revascularization, and Myofiber Regeneration in Skeletal Muscle Following Contusion Injury

“…Heat-induced antigen retrieval was performed using trisodium citrate buffer (Sigma-Aldrich) for 40 min at 70°C in an oven (Cole-Parmer StableTemp oven, Sydney, Australia). The slides were incubated overnight at 4°C with the following primary antibodies: mouse monoclonal anti-rat granulocyte (HIS48, 1:50; BD Pharmingen, San Diego, CA, USA) to identify neutrophils; mouse monoclonal anti-CD68 (ED1) (1:500; Abcam, Cambridge, MA, USA) to identify macrophages; rabbit polyclonal anti-human VEGF A-20 (sc-152, 1:500; Santa Cruz Biotechnology, Santa Cruz, CA, USA) as a proangiogenic factor; rabbit monoclonal anti-CD34 (EP373Y, 1:500; Abcam) and rabbit polyclonal anti-human von Willebrand Factor (vWF) (ready-to-use; Dako, Carpinteria, CA, USA) to identify endothelial cells associated with capillaries (Qu et al, 1997; Niiyama et al, 2003; Fujino et al, 2005; Wiik et al, 2005; Ho et al, 2006; Hollemann et al, 2008); and mouse monoclonal anti-nestin (Rat-401, 1:400; Santa Cruz Biotechnology) as a marker of maturing endothelial cells in muscle (Cizkova et al, 2009b). The slides were then incubated for 40 min with a goat anti-mouse and anti-rabbit secondary antibody conjugated with horseradish peroxidase (Dako).…”