Potential Roles of Vascular Endothelial Growth Factor During Skeletal Muscle Hypertrophy.

Vascular endothelial growth factor (VEGF) deletion in adult mouse muscle fibers contributes to impaired contractile and muscular adaptations to a hypertrophic stimulus suggesting a critical role in adult muscle growth. This review explores the hypothesis that VEGF is essential for adult muscle growth by impacting inflammatory processes, satellite-endothelial cell interactions, and contractile protein accumulation by functioning within known hypertrophic signaling pathways including insulin-like growth factor-1 (IGF-1-Akt) and Wnt-ß-catenin.

Skeletal myofiber VEGF is necessary for myogenic and contractile adaptations to functional overload of the plantaris in adult mice.

The ability to enhance muscle size and function is important for overall health. In this study, skeletal myofiber vascular endothelial growth factor (VEGF) was hypothesized to regulate hypertrophy, capillarity, and contractile function in response to functional overload (FO). Adult myofiber-specific VEGF gene-ablated mice (skmVEGF(-/-)) and wild-type (WT) littermates underwent plantaris FO or sham surgery (SHAM).

Effect of HSP25 loss on muscle contractile function and running wheel activity in young and old mice.

Aging is associated with an adverse decline in muscle function, often manifesting as decreased strength and increased muscle fatigability that negatively affects the overall health of the elderly. Heat shock proteins (HSPs), a family of stress inducible proteins known to protect cells from damage, are highly induced in muscle cells following exercise, but both basal and inducible levels decline with age. Utilizing young and old mice lacking HSP25 (Hsp25(-/-)) we tested the hypothesis that HSP25 is required to maintain normal muscle function and that age related decreases in HSP25 directly contribute to declining muscle function.

Effects of glutamine supplementation on muscle function and stress responses in a mouse model of spinal cord injury.

Spinal cord injury (SCI) results in loss of muscle function due to rapid breakdown of contractile proteins. Glutamine supplementation improves clinical outcomes, but its effects on muscle function after SCI are unknown. The benefits of glutamine in non-skeletal muscle tissues involve elevated heat shock protein (Hsp)70 and Hsp25, but the muscle response may differ because it is the largest contributor to plasma glutamine.

Statin-associated changes in skeletal muscle function and stress response after novel or accustomed exercise.

Introduction: The most common side effect of statins, myopathy, is more likely in exercisers. We investigated the interaction of statin treatment with novel vs. accustomed exercise on muscle function, heat shock protein (Hsp) expression, and caspase activation.

The α₇β₁-integrin increases muscle hypertrophy following multiple bouts of eccentric exercise.

Mechanical stimuli increase skeletal muscle growth in a mammalian target of rapamycin (mTOR)- and p70(S6K)-dependent manner. It has been proposed that costameric proteins at Z bands may sense and transfer tension to these initiators of protein translation, but few candidates have been identified. The purpose of this study was to determine whether a role exists for the α(7)-integrin in the activation of hypertrophic signaling and growth following eccentric exercise training.

The α7β1-integrin accelerates fiber hypertrophy and myogenesis following a single bout of eccentric exercise.

The α(7)β(1)-integrin is a heterodimeric transmembrane protein that adheres to laminin in the extracellular matrix, representing a critical link that maintains structure in skeletal muscle. In addition to preventing exercise-induced skeletal muscle injury, the α(7)-integrin has been proposed to act as an intrinsic mechanosensor, initiating cellular growth in response to mechanical strain. The purpose of this study was to determine the extent to which the α(7)-integrin regulates muscle hypertrophy following eccentric exercise.

Statin-associated myopathy and its exacerbation with exercise.

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are a common and effective treatment for hypercholesterolemia, with a low overall rate of side-effects. The most common complication is some degree of skeletal muscle myopathy, ranging from painless serum creatine kinase elevations to rhabdomyolysis. Unfortunately, the likelihood and/or severity of complications increases with the combination of statin treatment and physical activity.

Early response of heat shock proteins to functional overload of the soleus and plantaris in rats and mice.

Heat shock proteins (HSPs) are important factors in the response of skeletal muscles to chronic increases or decreases in activation and loading. The purpose of this study was to compare species-, time- and muscle-dependent changes in protein expression of Hsp20, Hsp25, αB-crystallin, Hsp72 and Hsp90 in response to functional overload (FO) in rats and mice. We compared protein levels of Hsp20, Hsp25, αB-crystallin, Hsp72 and Hsp90 in soleus and plantaris in baseline conditions and following 0.

Acute vascular endothelial growth factor expression during hypertrophy is muscle phenotype specific and localizes as a striated pattern within fibres.

Skeletal muscle hypertrophy requires the co-ordinated expression of locally acting growth factors that promote myofibre growth and concurrent adaptive changes in the microvasculature. These studies tested the hypothesis that vascular endothelial growth factor (VEGF) and heparin-binding epidermal growth factor (HB-EGF) expression are upregulated during the early stages of compensatory muscle growth induced by chronic functional overload (FO). Bilateral FO of the plantaris and soleus muscles was induced for 3 or 7 days in the hindlimbs of adult female Sprague-Dawley rats (n = 5 per group) and compared with control (non-FO) rats.

Glutamine preserves skeletal muscle force during an inflammatory insult.

The purpose of this study was to test the hypothesis that acute glutamine (GLN) supplementation can counteract skeletal muscle contractile dysfunction occurring in response to inflammation by elevating muscle heat shock protein (Hsp) expression and reducing inflammatory cytokines. Mice received 5 mg/kg lipopolysaccharide (LPS) concurrently with 1 g/kg GLN or vehicle treatments. Plantarflexor isometric force production was measured at 2 hours post-injection.

Contribution of IL-6 to the Hsp72, Hsp25, and alphaB-crystallin [corrected] responses to inflammation and exercise training in mouse skeletal and cardiac muscle.

The heat shock proteins (Hsps) Hsp72, Hsp25, and alphaB-crystallin (alphaB C) [corrected]may protect tissues during exercise and/or inflammatory insults; however, no studies have investigated whether exercise training increases both basal and inflammation-induced expression of these Hsps in skeletal or cardiac muscle. IL-6 is produced by muscle during both exercise and inflammation and has been shown to modulate Hsp expression. These studies tested the hypothesis that voluntary wheel running (RW) increases basal and inflammation-induced Hsp72, Hsp25, and alphaB C [corrected] protein through an IL-6-dependent mechanism.

Exaggerated expression of skeletal muscle-derived interleukin-6, but not TNFalpha, in mice lacking interleukin-10.

IL-10 reduces cytokine expression in non-muscle tissues, but its effect on skeletal muscle remains undefined. Therefore, we tested the hypothesis that endogenous IL-10 acts to reduce cytokines in the gastrocnemius muscle by comparing IL-6 and TNFalpha expression in wild-type (IL-10(+/+)) and IL-10 deficient (IL-10(-/-)) mice following an inflammatory insult induced by peripheral LPS. IL-6 mRNA expression increased following LPS for both IL-10(+/+) and IL-10(-/-) mice; the response was greater and prolonged in IL-10(-/-) mice.

PAX3/7 expression coincides with MyoD during chronic skeletal muscle overload.

Paired box (Pax) proteins 3 and 7 are key determinants for embryonic skeletal muscle development by initiating myogenic regulatory factor (MRF) gene expression. We show that Pax3 and 7 participate in adult skeletal muscle plasticity during the initial responses to chronic overload (< or =7 days) and appear to coordinate MyoD expression, a member of the MRF family of genes. Pax3 and 7 mRNA were higher than control within 12 h after initiation of overload, preceded the increase in MyoD mRNA on day 1, and peaked on day 2.

Time-dependent changes in caspase-3 activity and heat shock protein 25 after spinal cord transection in adult rats.

Chronic reductions in muscle activation and loading are associated with decreased heat shock protein 25 (Hsp25) expression and phosphorylation (pHsp25) which, in turn, may contribute to elevated caspase-3-mediated muscle protein breakdown. Thus, the purpose of the present study was to determine whether there are any changes in Hsp25, pHsp25 and caspase-3 activity among rat muscles having different fibre type compositions and functions [soleus, adductor longus (AL), plantaris and tibialis anterior (TA)] at 0 (control), 1, 8 or 28 days after a complete spinal cord transection (ST). The Hsp25 levels were unaffected on days 1 and 8 in all muscles, except for a significant reduction on day 8 in plantaris.

Modulation of HSP25 and TNF-alpha during the early stages of functional overload of a rat slow and fast muscle.

Early events in response to abrupt increases in activation and loading with muscle functional overload (FO) are associated with increased damage and inflammation. Heat shock protein 25 (HSP25) may protect against these stressors, and its expression can be regulated by muscle loading and activation. The purpose of this study was to investigate the responses of HSP25, phosphorylated HSP25 (pHSP25), and tumor necrosis factor-alpha (TNF-alpha) during FO of the slow soleus and fast plantaris.

Regulation of HSP25 expression and phosphorylation in functionally overloaded rat plantaris and soleus muscles.

Functional overload (FO) is a powerful inducer of muscle hypertrophy and both oxidative and mechanical stress in muscle fibers. Heat shock protein 25 (HSP25) may protect against both of these stressors, and its expression can be regulated by changes in muscle loading and activation. The primary purpose of the present study was to test the hypothesis that chronic FO increases HSP25 expression and phosphorylation (pHSP25) in hypertrophying rat hindlimb muscle.

Inactivity-induced modulation of Hsp20 and Hsp25 content in rat hindlimb muscles.

Denervation decreases small heat shock protein (HSP) content in the rat soleus muscle; however, it is unknown whether this change is due to inactivity or absence of a nerve-muscle connection. Spinal cord isolation (SI) is a model of inactivity with an intact neuromuscular connection. After 7 days of SI, Hsp20 and Hsp25 levels in the soleus, plantaris, and adductor longus muscles were lower than in control rats, whereas Hsp20 was unchanged and Hsp25 increased in the tibialis anterior.