Pericyte Degeneration and Basement Membrane Thickening in Skeletal Muscle Capillaries of Human Diabetics

Abstract

Pericyte distribution and capillary dimensions were determined in tissue obtained at autopsy from human pectoral, abdominal, quadriceps femoris, and gastrocnemius muscle of 20 diabetics and 20 age- and sex-matched nondiabetics. Tissue was processed for electron microscopy, and morphometric data obtained from electron micrographs were used to calculate capillary circumference, the percentage of capillary circumference covered by pericytes, and capillary basement membrane width (CBMW). The numbers of vessels containing pericytes and the number of pericyte processes per vessel were tabulated as indices of pericyte distribution along capillaries. The presence of cellular debris within capillary basement membranes was tabulated as an index of pericyte necrosis. Capillary circumference did not differ for controls and diabetics and did not vary between muscles from either group. CBMW was consistently thicker in diabetics than in controls and differences were greatest in lower extremity muscles. Pericytes were associated with virtually all vessels in lower extremity muscles of both normal and diabetic subjects. Although no differences were observed between controls and diabetics for each muscle examined, pericyte circumferential coverage of capillaries, as well as numbers of pericyte processes per capillary, increased significantly in the direction of head to foot for both controls and diabetics, paralleling increases in CBMW. Pericyte debris within capillary basement membranes also increased significantly in the direction of head to foot in both controls and diabetics and, in addition, occurred much more frequently in diabetics than in controls, with the greatest differences present in lower extremity muscles. These observations indicate that pericyte frequency and coverage of capillaries vary between different skeletal muscles, but not between controls and diabetics. These findings, coupled with the increased frequency of pericyte debris within capillary basement membranes of diabetics, suggest that: (1) pericyte degeneration and turnover are increased in skeletal muscle capillaries of diabetics, arid (2) pericyte degeneration is not limited to the retina in diabetes mellitus. A strong correlation between the presence of pericyte debris and capillary basement membrane thickening suggests that both may be linked to a common pathogenetic factor.