Importance of Anti‐angiogenic Factors in the Regulation of Skeletal Muscle Angiogenesis

Olfert, I. Mark; Birot, Olivier

doi:10.1111/j.1549-8719.2011.00092.x

Cited by 67 publications

(99 citation statements)

References 130 publications

(182 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the PLT, elevated muscle capillarity occurred in the presence of decreased basal TSP-1 expression and little or no increase in VEGF, suggesting that TSP-1 may also be playing an important role, at least in the PLT of MM mice. Despite the differences in these individual muscles, there is growing evidence that physiological regulation of angiogenesis is dependent on the balance between positive and negative angiogenic proteins such that the ratio of VEGF to TSP-1 expression may actually be more important than their individual expression levels per se (Olfert & Birot, 2011). The present results support the notion of an altered balance leading to capillary adaptation, with the notable exception of the PLT muscle in Non-MM mice.…”

Section: Basal Expression Of Vegf and Tsp-1 Correlates With Elevated supporting

confidence: 79%

“…VEGF) and negative (e.g. TSP-1) angiogenic factors (Hanahan & Folkman, 1996;Olfert & Birot, 2011). This altered balance would be another elegant way that the MM mice are genetically more able to adapt to an exercise stimulus.…”

Section: Genetic Background May Influence Angiogenic Responses To Acumentioning

confidence: 99%

“…One explanation for this discrepancy may be that other angiogenic regulators (such as endostatin, angiopoetins and their receptors, matrix metalloproteinases) are also playing a role, but are not accounted for in this study. Indeed, while we focused on VEGF and TSP-1 because of their recognized prominence in effecting changes in the skeletal muscle vascular bed, it is entirely possible (and likely) that other regulators also contribute to the basal angiogenic state (Olfert & Birot, 2011).…”

Section: Basal Expression Of Vegf and Tsp-1 Correlates With Elevated mentioning

confidence: 99%

See 2 more Smart Citations

Expression of angiogenic regulators and skeletal muscle capillarity in selectively bred high aerobic capacity mice

Audet

Meek

Garland

et al. 2011

Experimental Physiology

Self Cite

View full text Add to dashboard Cite

Selective breeding for high voluntary wheel running in untrained mice has resulted in a 'mini muscle' (MM) phenotype, which has increased skeletal muscle capillarity compared with muscles from non-selected control lines. Vascular endothelial growth factor (VEGF) and thrombospondin-1 (TSP-1) are essential mediators of skeletal muscle angiogenesis; thus, we hypothesized that untrained MM mice with elevated muscle capillarity would have higher basal VEGF expression and lower basal TSP-1 expression, and potentially an exaggerated VEGF response to acute exercise. We examined skeletal muscle morphology and skeletal muscle protein expression of VEGF and TSP-1 in male mice from two (untrained) mouse lines selectively bred for high exercise capacity (MM and Non-MM), as well as one non-selected control mouse line (normal aerobic capacity). In the MM mice, gastrocnemius (GA) and plantaris (PLT) muscle capillarity (i.e. capillary-to-fibre ratio and capillary density) were greater compared with control mice (P < 0.05). In Non-MM mice, only muscle capillarity in PLT was greater than in control mice (P < 0.001). The soleus (SOL) showed no statistical differences in muscle capillarity among groups. In the GA, MM mice had 58% greater basal VEGF (P < 0.05), with no statistical difference in basal TSP-1 when compared with control mice. In the PLT, MM mice had a 79% increase in basal VEGF (P < 0.05) and a 39% lower basal TSP-1 (P < 0.05) compared with the control animals. Non-MM mice showed no difference in basal VEGF in either the GA or the PLT compared with control mice. In contrast, basal TSP-1 was elevated in the PLT, but not in the GA, of Non-MM mice compared with control mice. Neither VEGF nor TSP-1 was significantly different in SOL muscle among the three mouse lines. In response to acute exercise, MM mice displayed a 41 and 28% increase (P < 0.05) in VEGF in the GA and PLT, respectively, whereas neither control nor Non-MM mice showed a significant VEGF response to acute exercise. In contrast, TSP-1 levels were decreased by 90% in GA (P < 0.05) but increased by 50% in PLT (P < 0.05) in response to acute exercise in MM mice. The SOL showed no response to exercise for either VEGF or TSP-1 for any of the mouse lines. These data, with the exception of the Non-MM plantaris muscle, suggest that elevated capillarity is associated with altered balance between positive and negative angiogenic regulators (i.e. VEGF versus TSP-1, respectively). Based on the greater capillarity and significant VEGF response to exercise in MM mice, these data suggest that VEGF expression may, at least in part, be genetically determined.

show abstract

Section: Basal Expression Of Vegf and Tsp-1 Correlates With Elevated supporting

confidence: 79%

Section: Genetic Background May Influence Angiogenic Responses To Acumentioning

confidence: 99%

Section: Basal Expression Of Vegf and Tsp-1 Correlates With Elevated mentioning

confidence: 99%

See 1 more Smart Citation

Expression of angiogenic regulators and skeletal muscle capillarity in selectively bred high aerobic capacity mice

Audet

Meek

Garland

et al. 2011

Experimental Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Current studies evaluating the angiogenic response to endurance training have focused on molecular mechanisms, including increased release of vascular endothelial growth factor (VEGF) from contracting muscle fibers (20) and decreased release of anti-angiogenic factors (21). In contrast, minimal information exists regarding the structural changes that occur within the capillary bed of the muscle following eccentric contractions, commonly performed during resistance training.…”

mentioning

confidence: 99%

“…Sprouting angiogenesis is a well-described adaptation that occurs in skeletal muscle in response to endurance exercise training, a response necessary to facilitate the delivery of oxygen and nutrients necessary to maintain long-duration exercise (21,32). Current studies evaluating the angiogenic response to endurance training have focused on molecular mechanisms, including increased release of vascular endothelial growth factor (VEGF) from contracting muscle fibers (20) and decreased release of anti-angiogenic factors (21).…”

mentioning

confidence: 99%

Mesenchymal stem cells contribute to vascular growth in skeletal muscle in response to eccentric exercise

Huntsman

Zachwieja

Zou

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

-The ␣ 7␤1-integrin is an adhesion molecule highly expressed in skeletal muscle that can enhance regeneration in response to eccentric exercise. We have demonstrated that mesenchymal stem cells (MSCs), predominantly pericytes, accumulate in muscle (mMSCs) overexpressing the ␣ 7B-integrin (MCK:␣7B; ␣7Tg) and contribute to new fiber formation following exercise. Since vascularization is a common event that supports tissue remodeling, we hypothesized that the ␣ 7-integrin and/or mMSCs may stimulate vessel growth following eccentric exercise. Wild-type (WT) and ␣ 7Tg mice were subjected to single or multiple (3 times/wk, 4 wk) bouts of downhill running exercise. Additionally, 1,1=-dioctadecyl-3,3,3=,3=-tetramethylindocarbocyanine perchlorate (DiI) -labeled mMSCs were intramuscularly injected into WT recipients. A subset of recipient mice were run downhill before injection to recapitulate the exercised microenvironment. While total number of CD31 ϩ vessels declined in both WT and ␣7Tg muscle following a single bout of exercise, the number of larger CD31 ϩ vessels with a visible lumen was preferentially increased in ␣7Tg mice following eccentric exercise training (P Ͻ 0.05). mMSC transplantation similarly increased vessel diameter and the total number of neuron-glial antigen-2 (NG2 ϩ ) arterioles postexercise. Secretion of arteriogenic factors from mMSCs in response to mechanical strain, including epidermal growth factor and granulocyte macrophage-colony stimulating factor, may account for vessel remodeling. In conclusion, this study demonstrates that the ␣ 7-integrin and mMSCs contribute to increased vessel diameter size and arteriolar density in muscle in response to eccentric exercise. The information in this study has implications for the therapeutic treatment of injured muscle and disorders that result in vessel occlusion, including peripheral artery disease.integrin; pericyte; remodeling; angiogenesis; arteriole INTEGRINS ARE TRANSMEMBRANE adhesion proteins comprised of noncovalently bound ␣-and ␤-subunits. Integrins form clusters and recruit cytoskeletal and cytoplasmic proteins to the cell membrane to provide a mechanism of communication between the outside and inside of the cell (10). In skeletal muscle, the ␣ 7 ␤ 1 -integrin is the predominant heterodimer based on high levels of protein expression, and its primary function is to ensure adhesion by providing a stabilizing link between the actin cytoskeleton and the external environment, specifically, laminin (6). Transgenic expression of the integrin in mouse muscle can suppress macrophage infiltration, sarcolemmal damage, and reductions in force following eccentric exercise (3, 4, 13). Our recently published work also suggests ␣ 7BX2 -integrin overexpression (MCK:␣ 7BX2 ; ␣ 7 Tg) can increase myogenesis, hypertrophic signaling, myofibrillar content, fiber cross-sectional area, muscle cross-sectional area, and maximal isometric force following single or multiple bouts of eccentric exercise (13, 34), a type of exercise that results in muscle lengthening during...

show abstract

Ultrastructure of Skeletal Muscles in Mice Lacking Muscle‐Specific VEGF Expression

Baum

Jentsch

Odriozola

et al. 2017

The Anatomical Record

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Importance of Anti‐angiogenic Factors in the Regulation of Skeletal Muscle Angiogenesis

Cited by 67 publications

References 130 publications

Expression of angiogenic regulators and skeletal muscle capillarity in selectively bred high aerobic capacity mice

Expression of angiogenic regulators and skeletal muscle capillarity in selectively bred high aerobic capacity mice

Mesenchymal stem cells contribute to vascular growth in skeletal muscle in response to eccentric exercise

Ultrastructure of Skeletal Muscles in Mice Lacking Muscle‐Specific VEGF Expression

Contact Info

Product

Resources

About