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 1 microm-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.
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 1 microm-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.
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