Ultrastructure of Skeletal Muscles in Mice Lacking Muscle-Specific VEGF Expression.

Abstract

Vascular endothelial growth factor-A (VEGF) influences several physiological processes including endothelial cell function, angiogenesis and maintenance of organ/tissue capillarity. While the functional aspects of VEGF were vigorously investigated, only little detail is known on structural integrity of skeletal muscle fibers and capillaries in mice lacking VEGF expression in their muscles. Therefore, we assessed systematically the architecture of the glycolytic plantaris and the oxidative soleus muscles obtained from muscle-specific VEGF knockout (mVEGF-KO, n = 7) mice and their wild-type (WT, n = 7) littermates by morphometry after transmission electron microscopy. The capillary/fiber ratio was lower (plantaris: -63.5%; soleus: -54.8%; P ≤ 0.05) in mVEGF-KO mice than in WT mice. In plantaris, quantification of volume density (Vv) of compartments revealed higher Vv of total mitochondria (+56.5%, P ≤ 0.05) as well as higher Vv-values for both intrafibrillar (+39%; P ≤ 0.05) and subsarcolemmal (+220%; P ≤ 0.05) mitochondrial pools in mVEGF-KO mice than WT mice. The capillary phenotype also differed (P ≤ 0.05) between the two mouse-strains: Vv (-17.4%), absolute area size (-19.1%) and thickness (-19.6%) of the endothelium layer were lower and Vv of capillary lumen (+15.1%) was higher in mVEGF-KO mice than in WT littermates. In soleus, mitochondrial Vv in fibers and the structural indicators specific to the capillary phenotype exhibited the same tendency in differences between the mouse strains without reaching statistical significance. Our morphometric analysis demonstrates that the lower capillary supply in plantaris of mVEGF-KO mice is accompanied by higher mitochondrial Vv in muscle fibers as well as lumen dilation and endothelium thinning of capillaries. These structural alterations were more pronounced in a glycolytic than an oxidative muscle. Anat Rec, 300:2239-2249, 2017. © 2017 Wiley Periodicals, Inc.