Arteriolization of capillaries and FGF-2 upregulation in skeletal muscles of patients with chronic peripheral arterial disease

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 mu 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 ill combination with a significant increase in sma-coverage indicate arteriolization of capillaries characteristic for chronic PAD, what. may be related to high FCF-2 expression in capillary endothelial cells.