Muscle activation as well as changes in peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) following high-intensity interval exercise (HIIE) were examined in young healthy men (n  = 8; age, 21.9±2.2 yrs; VO2peak, 53.1±6.4 ml/min/kg; peak work rate, 317±23.5 watts). On each of 3 visits HIIE was performed on a cycle ergometer at a target intensity of 73, 100, or 133% of peak work rate. Muscle biopsies were taken at rest and three hours after each exercise condition. Total work was not different between conditions (∼730 kJ) while average power output (73%, 237±21; 100%, 323±26; 133%, 384±35 watts) and EMG derived muscle activation (73%, 1262±605; 100%, 2089±737; 133%, 3029±1206 total integrated EMG per interval) increased in an intensity dependent fashion. PGC-1α mRNA was elevated after all three conditions (p<0.05), with a greater increase observed following the 100% condition (∼9 fold, p<0.05) compared to both the 73 and 133% conditions (∼4 fold). When expressed relative to muscle activation, the increase in PGC-1α mRNA for the 133% condition was less than that for the 73 and 100% conditions (p<0.05). SIRT1 mRNA was also elevated after all three conditions (∼1.4 fold, p<0.05), with no difference between conditions. These findings suggest that intensity-dependent increases in PGC-1α mRNA following submaximal exercise are largely due to increases in muscle recruitment. As well, the blunted response of PGC-1α mRNA expression following supramaximal exercise may indicate that signalling mediated activation of PGC-1α may also be blunted. We also indentify that increases in PDK4, SIRT1, and RIP140 mRNA following acute exercise are dissociated from exercise intensity and muscle activation, while increases in EGR1 are augmented with supramaximal HIIE (p<0.05).

Although the genetic basis of PAH is known in some cases, the underlying mechanisms that link loss-of-function mutations in BMPR2 with the development of PAH and its characteristic lung vascular lesions are still unclear. Clinical Perspective on p 2135EC injury and apoptosis are key triggers for the development of PAH. Treatment of rats with a vascular endothelial growth factor receptor antagonist, SU5416, together with a period of chronic hypoxia, 9,10 results in a model of severe, Background-Pulmonary arterial hypertension (PAH) is a lethal disease characterized by excessive proliferation of pulmonary vascular endothelial cells (ECs). Hereditary PAH (HPAH)is often caused by mutations in the bone morphogenetic protein receptor type 2 gene (BMPR2). However, the mechanisms by which these mutations cause PAH remain unclear. Therefore, we screened for dysregulated proteins in blood-outgrowth ECs of HPAH patients with BMPR2 mutations compared with healthy control subjects. Methods and Results-A total of 416 proteins were detected with 2-dimensional PAGE in combination with liquid chromatography/tandem mass spectrometry analysis, of which 22 exhibited significantly altered abundance in bloodoutgrowth ECs from patients with HPAH. One of these proteins, translationally controlled tumor protein (TCTP), was selected for further study because of its well-established role in promoting tumor cell growth and survival. Immunostaining showed marked upregulation of TCTP in lungs from patients with HPAH and idiopathic PAH, associated with remodeled vessels of complex lesions. Increased TCTP expression was also evident in the SU5416 rat model of severe and irreversible PAH, associated with intimal lesions, colocalizing with proliferating ECs and the adventitia of remodeled vessels but not in the vascular media. Furthermore, silencing of TCTP expression increased apoptosis and abrogated the hyperproliferative phenotype of blood-outgrowth ECs from patients with HPAH, raising the possibility that TCTP may be a link in the emergence of apoptosis-resistant, hyperproliferative vascular cells after EC apoptosis. The critical role of EC apoptosis as a trigger in experimental models of PAH is also supported by the efficacy of EC growth and survival factors (eg, vascular endothelial growth factor and angiopoietin-1) in monocrotalineinduced PAH. 13,14 The possible relevance of this paradigm for human PAH is supported by the observation that silencing of BMPR2 15 or overexpression of mutant BMPR2 in human ECs 16 increases apoptosis. Conclusion-ProteomicThe lack of availability of lung tissue from early-stage disease represents a significant limitation for unraveling the initiating mechanisms of human PAH. The selection pressures exerted on resident lung ECs make it is difficult to separate the direct effects of BMPR2 mutations on EC biology from reactive changes in response to the abnormal growth and survival influences of the lung PAH milieu. Recently, it has been recognized that cells with an endothelial phenotype nearly identical to that...

Together, these results indicate that reducing SIT work-interval duration from 30 to 15 s had no impact on training-induced increases in aerobic or anaerobic power, or on increases in lactate threshold (absolute) and critical power.

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