title: Resistance vessel remodeling and reparative angiogenesis in the microcirculatory bed of long-term denervated skeletal muscles.
abstract: In denervated skeletal muscles, atrophy of muscle fibers and interstitial fibrosis are associated with alterations within the vascular bed. Our study has placed particular emphasis on changes occurring in resistance vessels and the microcirculatory bed of rat hindlimb skeletal muscles that had been denervated for 25 months. We found that the tunica media of the majority of long-term denervated resistance vessels undergoes deterioration. In small intramuscular arteries and arterioles, atrophic vascular smooth muscle cells (vSMCs) enclosed in a thick basal lamina are separated by expanded extracellular space. The remodeling and sclerotic changes in the arterial wall occasionally result in deformation of the lumen. It was also found that the microcirculatory bed undergoes significant alterations. In 25-month denervated extensor digitorum longus muscle, the capillary-to-fiber ratio is only 0.13 +/- 0.01 and the mean number of capillaries per fascicle decreases almost ninefold compared to contralateral control muscle. Ultrastructural findings demonstrate that 24.67 +/- 0.48% of capillaries examined in the chronically denervated fascicles show structural features typical for capillary regeneration. In addition, long cytoplasmic extensions of pericytes might develop a layer completely encircling the capillary endothelium. In pre- and postcapillary segments of the microcirculatory bed, some perivascular cells possess a phenotype that is intermediate between that of pericytes and atrophic vSMCs. RT-PCR and/or Western blot analyses showed that molecules participating in angiogenesis are detected in 25-month denervated skeletal muscle. We hypothesize that despite the fact that the microcirculatory bed of chronically denervated muscle undergoes significant reduction it still sustains the capacity for reparative capillary growth.
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA. ededkof@umich.edu
authors.forename: E I
authors.initials: EI
authors.lastname: Dedkov
authors.forename: T Y
authors.initials: TY
authors.lastname: Kostrominova
authors.forename: A B
authors.initials: AB
authors.lastname: Borisov
authors.forename: B M
authors.initials: BM
authors.lastname: Carlson
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002196:Capillaries / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D008222:Lymphokines / Q000096:biosynthesis; D008833:Microcirculation; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000294:innervation* / Q000648:ultrastructure; D009130:Muscle, Smooth / Q000166:cytology / Q000648:ultrastructure; D018919:Neovascularization, Physiologic; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D012313:RNA / Q000378:metabolism; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis; D017978:Receptors, Growth Factor / Q000096:biosynthesis; D040262:Receptors, Vascular Endothelial Growth Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000502:physiology; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D012313:RNA; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1