Endoneurial microvascular abnormalities of sural nerve in non-diabetic chronic atherosclerotic occlusive disease

Neuropathic abnormalities are found in chronically ischaemic limbs associated with non-diabetic atherosclerotic peripheral vascular disease (PVD). In chronic ischaemic neuropathy, microvascular alterations play a key role in its development. We undertook morphometric assessment of endoneurial microvessels in the sural nerves, taken from severely ischaemic amputated legs in nine chronic non-diabetic PVD. These subjects had threatened ischaemic limbs and revealed clinical, physiological and pathological evidence of neuropathy. For comparison, sural nerves taken from amputated legs due to non-ischaemic disorders (n=4) and chronic PVD associated with diabetes (n=3) were also assessed. We evaluated the areas of vascular lumen, endothelial cells and whole vessel, as well as the percentage of closed capillaries. Endothelial area of sural nerve microvessels in non-diabetic PVD nerves was significantly greater than in non-ischaemic control nerves. Periendothelial cell area containing pericytes and basement membranes was also significantly increased in non-diabetic PVD nerves when compared with control nerves. Vascular lumen area was significantly less in non-diabetic PVD nerves than in non-ischaemic control nerves. Endoneurial microvessels in diabetic PVD nerves showed similar results: thickened vessel wall and smaller lumen. Periendothelial area in diabetic nerves was significantly greater than in non-diabetic PVD nerves. We demonstrated swollen endothelial cells and increased periendothelial area associated with narrowed lumen in sural nerve endoneurial microvessels of severe chronic PVD. Basement membrane reduplication of endoneurial capillaries was seen in non-diabetic PVD nerves. These microvascular abnormalities could play an important role in the development of chronic ischaemic neuropathy in PVD limbs.