Abstract
Objective: Microvascular changes in ischemic skeletal muscle are described derived from patients with long-lasting peripheral arterial disease (PAD).
Methods: Skeletal muscles from the lower limb of 17 patients (obtained after amputation) with chronic PAD and 4 asymptomatic controls (obtained from biopsies after bypass surgery) were evaluated by electron microscopy and immunohistochemistry.
Results: The capillaries in skeletal muscles of PAD patients were surrounded by a more than 1μ m-thick coat, which was positively stained for basement membrane pericapillary coat collagen type IV. Thickness of the coat correlated with presence of PAD (p < .0001), and less strongly with diabetes mellitus (p = .023) and age of patients (p = .019). The majority of the capillaries in skeletal muscles of PAD patients (71.1 ± 15.3%) were covered with cells positive for smooth muscle cell actin (sma) as compared to samples from asymptomatic controls (22.8% ± 9.6%; p < .0001) suggesting advanced arteriolization. Semiquantitative analysis revealed that patients with PAD demonstrate a higher expression of FGF-2 in capillary endothelial cells (67.8 ± 17.5%) as compared to controls (10.2 ± 8.4%; p < .0001), whereas VEGF immunoreactivity was only occasionally present in extravascular cells.
Conclusion: Thickened collagen type IV-positive basement membranes in combination with a significant increase in sma-coverage indicate arteriolization of capillaries characteristic for chronic PAD, what may be related to high FGF-2 expression in capillary endothelial cells.
This study was generously supported by a grant from Centelion (Gencell), France. We thank Bettina de Breuyn and Krystyna Sala for skillful technical support and Jolanda Voegele for careful collection of clinical data. Statistical support was given by B. Gahl, Swiss Cardiovascular Center, University Hospital, Bern.