The basement membrane (BM) surrounding capillaries in skeletal muscles varies physiologically in thickness according to age, physical fitness and anatomical site in humans. Furthermore, the peri-capillary BM thickness (CBMT) increases pathophysiologically during several common disease states, including peripheral arterial disease and diabetes mellitus. This review on CBM-thickening in human skeletal muscles is two-pronged. Firstly, it addresses the advantages/disadvantages of grid- and tablet-based measuring and morphometric techniques that are implemented to assess the CBMT on transmission electron micrographs. Secondly, it deals with the biology of CBM-thickening in skeletal muscles, particularly its possible causes, molecular mechanisms and functional impact. CBM-thickening is triggered by several physical factors including diabetes-associated glycation, hydrostatic pressure and inflammation. Increased biosynthesis of type IV collagen expression or repetitive cycles in pericyte or endothelial cell degeneration/proliferation appear to be most critical for CBM accumulation. A thickened CBM obviously poses a greater barrier for diffusion, lowers the microvascular elasticity and impedes transcytosis of inflammatory cells. Our own morphometric data reveal the CBM-enlargement to be not accompanied by the pericyte coverage. Owing to an overlap or redundancy in the capillary supply, CBM-thickening in skeletal muscles might not be such a devastating occurrence as in organs with endarterial circulation (e.g. kidney and retina). CBM growth in skeletal muscles can be reversed by training or administration of anti-diabetic drugs. In conclusion, CBM-thickening in skeletal muscles is a microvascular remodeling process by which metabolic, hemodynamic and inflammatory forces are integrated together and which could play a hitherto underestimated role in etiology/progression of human diseases.
- Basement membrane
- Skeletal muscle
- Transmission electron microscopy
- Copyright © 2016, American Journal of Physiology - Heart and Circulatory Physiology