Background and Purpose-Stroke survivors experience disproportionate muscle atrophy and other detrimental tissue composition changes on the paretic side. The purpose was to determine whether myostatin levels are higher in paretic vs nonparetic muscle and the effects of resistive training (RT) on paretic and nonparetic mid-thigh muscle composition and myostatin mRNA expression in stroke survivors. Methods-Fifteen stroke survivors (50 -76 years) underwent bilateral multi-slice thigh CT scanning from the knee to the hip, bilateral vastus lateralis skeletal muscle tissue biopsies, a total body scan by dual-energy X-ray absorptiometry, and 1-repetition maximum strength test before and after a 12-week, (3 times/week) RT intervention. Results-Total body fat mass and fat-free mass did not change. Bilateral leg press and leg extension 1-repetition maximum strength increased 31% to 56% with RT (PϽ0.001). Paretic and nonparetic muscle area of the mid-thigh increased 13% (PϽ0.01) and 9% (PϽ0.05), respectively, after RT. Muscle attenuation of the mid-thigh increased 15% and 8% (both PϽ0.01) in the paretic and nonparetic thigh, respectively, representing reduced intramuscular fat. Muscle volume increased 14% (PϽ0.001) in the paretic thigh and 16% (PϽ0.05) in the nonparetic thigh after RT. Myostatin mRNA expression levels were 40% higher in the paretic than nonparetic muscle (Pϭ0.001) at baseline and decreased 49% in the paretic muscle (PϽ0.005) and 27% in the nonparetic muscle (Pϭ0.06) after RT. Conclusions-Progressive RT stimulates significant muscle hypertrophy and intramuscular fat reductions in disabled stroke survivors. The increased myostatin mRNA in the paretic thigh and reduction with RT imply an important regulatory role for myostatin after stroke. (Stroke. 2011;42:416-420.)

Intramuscular signaling and glucose transport mechanisms contribute to improvements in insulin sensitivity after aerobic exercise training. This study tested the hypothesis that increases in skeletal muscle capillary density (CD) also contribute to exercise-induced improvements in whole-body insulin sensitivity (insulin-stimulated glucose uptake per unit plasma insulin [M/I]) independent of other mechanisms. The study design included a 6-month aerobic exercise training period followed by a 2-week detraining period to eliminate short-term effects of exercise on intramuscular signaling and glucose transport. Before and after exercise training and detraining, 12 previously sedentary older (65 ± 3 years) men and women underwent research tests, including hyperinsulinemic-euglycemic clamps and vastus lateralis biopsies. Exercise training increased Vo2max (2.2 ± 0.2 vs. 2.5 ± 0.2 L/min), CD (313 ± 13 vs. 349 ± 18 capillaries/mm2), and M/I (0.041 ± 0.005 vs. 0.051 ± 0.007 μmol/kg fat-free mass/min) (P < 0.05 for all). Exercise training also increased the insulin activation of glycogen synthase by 60%, GLUT4 expression by 16%, and 5′ AMPK-α1 expression by 21%, but these reverted to baseline levels after detraining. Conversely, CD and M/I remained 15% and 18% higher after detraining, respectively (P < 0.05), and the changes in M/I (detraining minus baseline) correlated directly with changes in CD in regression analysis (partial r = 0.70; P = 0.02). These results suggest that an increase in CD is one mechanism contributing to sustained improvements in glucose metabolism after aerobic exercise training.

Non-technical summary Circulating angiogenic cells (CACs) repair and maintain the vascular endothelium. CACs are responsive to lifestyle factors such as diet and physical activity. For example, their capacity to regenerate the endothelium is impaired in cardiovascular disease patients, whereas exercise training can improve CAC function. In this study, we examined the effects of a high-fat meal with and without prior endurance exercise on several molecular aspects of CAC function, including levels of reactive oxygen species (ROS), nitric oxide (NO), intracellular lipids, and gene expression. Our results indicated that the high-fat meal induced significant oxidative stress (i.e. ROS production) in the CACs that expressed the cell surface protein CD31. However, when subjects performed a single bout of exercise on the prior day, the meal had no effect on ROS in CD31 + cells. Therefore, we concluded that prior exercise prevents the oxidative stress induced by a high-fat meal in CD31 + CACs.Abstract We hypothesized that prior exercise would prevent postprandial lipaemia (PPL)-induced increases in intracellular reactive oxygen species (ROS) in three distinct circulating angiogenic cell (CAC) subpopulations. CD34 + , CD31 + /CD14 − /CD34 − , and CD31 + /CD14 + /CD34 − CACs were isolated from blood samples obtained from 10 healthy men before and 4 h after ingesting a high fat meal with or without ∼50 min of prior endurance exercise. Significant PPL-induced increases in ROS production in both sets of CD31 + cells were abolished by prior exercise. Experimental ex vivo inhibition of NADPH oxidase activity and mitochondrial ROS production indicated that mitochondria were the primary source of PPL-induced oxidative stress. The attenuated increases in ROS with prior exercise were associated with increased antioxidant gene expression in CD31 + /CD14 − /CD34 − cells and reduced intracellular lipid uptake in CD31 + /CD14 + /CD34 − cells. These findings were associated with systemic cardiovascular benefits of exercise, as serum triglyceride, oxidized low density lipoprotein-cholesterol, and plasma endothelial microparticle concentrations were lower in the prior exercise trial than the control trial. In conclusion, prior exercise completely prevents PPL-induced increases in ROS in CD31 + /CD14 − /CD34 − and CD31 + /CD14 + /CD34 − cells. The mechanisms underlying the effects of exercise on CAC function appear to vary among specific CAC types.

In its role as an endothelial cell proliferation and migration factor, vascular endothelial growth factor (VEGF) can affect peripheral circulation and therefore impact maximal oxygen consumption (Vo2 max). Because of the role of VEGF, and because variation in the VEGF gene has the ability to alter VEGF gene expression and VEGF protein level, we hypothesized that VEGF gene polymorphisms are related to VEGF gene expression in human myoblasts and Vo2 max before and after aerobic exercise training. We analyzed the effects of the VEGF -2578/-1154/-634 promoter region haplotype on VEGF gene expression by using a luciferase reporter assay in cultured human myoblasts and found that the AAG and CGC haplotypes resulted in significantly higher hypoxia-stimulated VEGF gene expression than the AGG and CGG haplotypes. Consistent with these results, we found that individuals with at least one copy of the AAG or CGC haplotype had higher Vo2 max before and after aerobic exercise training than did subjects with only the AGG and/or CGG haplotype. In conclusion, we found that VEGF -2578/-1154/-634 haplotype impacts VEGF gene expression in human myoblasts and is associated with Vo2 max. These results have potential implications for aerobic exercise training and may prove relevant in the study of pathological conditions that can be affected by angiogenesis, such as coronary artery disease and peripheral artery disease.

These findings suggest that low skeletal muscle capillarization is one factor that may contribute to sarcopenia and reduced exercise capacity in older adults by limiting diffusion of substrates, oxygen, hormones, and nutrients. Strategies to prevent the aging-related decline in skeletal muscle capillarization may help to prevent or slow the progression of sarcopenia and its associated functional declines in generally healthy older adults.

OBJECTIVETranscapillary transport of insulin is one determinant of glucose uptake by skeletal muscle; thus, a reduction in capillary density (CD) may worsen insulin sensitivity. Skeletal muscle CD is lower in older adults with impaired glucose tolerance (IGT) compared with those with normal glucose tolerance and may be modifiable through aerobic exercise training and weight loss (AEX+WL). We tested the hypothesis that 6-month AEX+WL would increase CD to improve insulin sensitivity and glucose tolerance in older adults with IGT.RESEARCH DESIGN AND METHODSSixteen sedentary, overweight-obese (BMI 27–35 kg/m2), older (63 ± 2 years) men and women with IGT underwent hyperinsulinemic-euglycemic clamps to measure insulin sensitivity, oral glucose tolerance tests, exercise and body composition testing, and vastus lateralis muscle biopsies to determine CD before and after 6-month AEX+WL.RESULTSInsulin sensitivity (M) and 120-min postprandial glucose (G120) correlated with CD at baseline (r = 0.58 and r = −0.60, respectively, P < 0.05). AEX+WL increased maximal oxygen consumption (VO2max) 18% (P = 0.02) and reduced weight and fat mass 8% (P < 0.02). CD increased 15% (264 ± 11 vs. 304 ± 14 capillaries/mm2, P = 0.01), M increased 21% (42.4 ± 4.0 vs. 51.4 ± 4.3 µmol/kg FFM/min, P < 0.05), and G120 decreased 16% (9.35 ± 0.5 vs. 7.85 ± 0.5 mmol/L, P = 0.008) after AEX+WL. Regression analyses showed that the AEX+WL-induced increase in CD independently predicted the increase in M (r = 0.74, P < 0.01) as well as the decrease in G120 (r = −0.55, P < 0.05).CONCLUSIONSSix-month AEX+WL increases skeletal muscle CD in older adults with IGT. This represents one mechanism by which AEX+WL improves insulin sensitivity in older adults with IGT.

AEX + WL is more efficacious than AEX for reducing LDM and glucose tolerance. The improvement in glucose tolerance may be partially mediated by decreases in LDM in older men.

Objective-The goal of this study is to determine whether C-reactive protein (CRP) gene variants affect baseline and training-induced changes in plasma CRP levels. Methods and Results-Sixty-three sedentary men and women aged 50 to 75 years old underwent baseline testing (VOmax, body composition, CRP levels). They repeated these tests after 24 weeks of exercise training while on a low-fat diet. The CRP ϩ219G/A variant significantly associated with CRP levels before and after training after accounting for the effects of demographic and biological variables. CRP Ϫ732A/G genotype was significantly related on a univariate basis to CRP levels after training. The CRP ϩ29T/A variant did not affect CRP levels before or after training. In regression analyses, the ϩ219 and Ϫ732 variants each had significant effects on CRP levels before and after training. Subjects homozygous for the common A/G Ϫ732/ϩ219 haplotype exhibited the highest CRP levels, and having the rare allele at either site was associated with significantly lower CRP levels. CRP levels decreased significantly with training (Ϫ0.38Ϯ0.18 mg/L; Pϭ0.03). However, none of the CRP variants was associated with the training-induced CRP changes. Conclusion-CRP ϩ219G/A and Ϫ732A/G genotypes and haplotypes and exercise training appear to modulate CRP levels. However, training-induced CRP reductions appear to be independent of genotype at these loci. Key Words: C-reactive protein Ⅲ genetics Ⅲ exercise training A therosclerosis, which is the main mechanism underlying most cardiovascular (CV) diseases, is now considered to be, at least partly, an inflammatory disorder. C-reactive protein (CRP) has been proposed as a marker of inflammation, 1 with lower CRP levels associated with reduced CV disease risk 2 and even slight CRP elevations associated with increased CV events. 1 Cross-sectional studies have found that CRP levels are lowest in those with the highest levels of habitual physical activity; 3 however, very few studies have assessed the impact of an exercise training intervention on CRP levels. 4 See pages 1743 and 1868Recent evidence indicates that common polymorphisms at the CRP gene locus affect CRP levels. 5,6 Four single nucleotide polymorphisms (SNPs) have been identified in the CRP gene: Ϫ732 A/G, an adenine/guanine transition in the promoter region of the CRP gene; 7 ϩ29 T/A, a thymine/adenine transversion in intron 1, 29-bp downstream (3Ј) of exon 1; ϩ1059 G/C, a silent guanine/cytosine transversion in the exon 2 coding region; 8 and ϩ219 G/A, a guanine/adenine transition in the 3Ј flanking sequence of the CRP gene, 219-bp downstream (3Ј) of exon 2. Because genetic variations affect the responses of other CV disease risk factors to exercise training, 9,10 it is possible that these CRP gene variants may interact with exercise training to differentially affect plasma CRP levels. Thus, we hypothesized that CRP levels at baseline and after 6 months of exercise training will differ among CRP genotype groups, CRP levels will decrease as a result of exercise training,...