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 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.


CONCLUSIONS
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.
Baum
Oliver
O
Institute of Anatomy, University of Bern, Switzerland. oliver.baum@ana.unibe.ch
Djonov
Valentin
V
Ganster
Murielle
M
Widmer
Matthias
M
Baumgartner
Iris
I
D000368:Aged; D000369:Aged, 80 and over; D001160:Arterioles / Q000473:pathology / Q000503:physiopathology*; D001485:Basement Membrane / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D002196:Capillaries / Q000503:physiopathology* / Q000648:ultrastructure; D002908:Chronic Disease; D024141:Collagen Type IV / Q000096:biosynthesis; D042783:Endothelial Cells / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis*; D006801:Humans; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000648:ultrastructure; D016491:Peripheral Vascular Diseases / Q000473:pathology / Q000503:physiopathology*; D015854:Up-Regulation
D024141:Collagen Type IV; D016222:Fibroblast Growth Factor 2