Heart transplant (HTx) recipients usually have reduced exercise capacity with reported VO 2peak levels of 50-70% predicted value. Our hypothesis was that highintensity interval training (HIIT) is an applicable and safe form of exercise in HTx recipients and that it would markedly improve VO 2peak.Secondarily, we wanted to evaluate central and peripheral mechanisms behind a potential VO 2peak increase. Forty-eight clinically stable HTx recipients >18 years old and 1-8 years after HTx underwent maximal exercise testing on a treadmill and were randomized to either exercise group (a 1-year HIIT-program) or control group (usual care). The mean ± SD age was 51 ± 16 years, 71% were male and time from HTx was 4.1 ± 2.2 years. The mean VO 2peak difference between groups at follow-up was 3.6 [2.0, 5.2] mL/kg/min (p < 0.001). The exercise group had 89.0 ± 17.5% of predicted VO 2peak versus 82.5 ± 20.0 in the control group (p < 0.001). There were no changes in cardiac function measured by echocardiography. We have demonstrated that a long-term, partly supervised and community-based HIIT-program is an applicable, effective and safe way to improve VO 2peak , muscular exercise capacity and general health in HTx recipients. The results indicate that HIIT should be more frequently used among stable HTx recipients in the future.Key words: Aerobic exercise, chronotropic response, heart transplantation, maximum oxygen uptake, muscle strength, VO 2peak Abbreviations: % HR max , percent of age-predicted maximum heart rate; AT, anaerobic threshold (ventilatory threshold); BIA, bioelectrical impedance analysis; CG, control group; CO, cardiac output; CRI, chronotropic response index; CRP, C-reactive protein; DXA, dual-emission X-ray absorptiometry; EG, exercise group; eGFR, estimated glomerular filtration rate; Hb, hemoglobin; HF, heart failure; HIIT, high-intensity interval training; HR, heart rate; HR max , maximum heart rate; HRQoL, health-related quality of life; HTx, heart transplant; J, Joule; LV, left ventricle; LVe', left ventricle early diastolic mitral annular velocity; LVEF, left ventricle ejection fraction; Nm, Newtonmeter; NT-proBNP, N-terminal prohormone of brain natriuretic peptide; RER, respiratory exchange ratio; RPE, rated perceived exertion; VAS scale, visual analog scale; VE max , maximum ventilation; VO 2peak , peak oxygen uptake.

Objective-Based on the emerging importance of the wingless (Wnt) pathways in inflammation and vascular biology, we hypothesized a role for Dickkopf-1 (DKK-1), a major modulator of Wnt signaling, in atherogenesis and plaque destabilization. Methods and Results-We report increased levels of DKK-1 in experimental (ApoE Ϫ/Ϫ mice) and clinical (patients with coronary artery disease ͓nϭ80͔ and patients with carotid plaque ͓nϭ47͔) atherosclerosis, both systemically (serum) and within the lesion, with particularly high levels in advanced and unstable disease. We identified platelets as an important cellular source of DKK-1 as shown by in vitro experiments and by immunostaining of thrombus material obtained at the site of plaque rupture in patients with acute ST-elevation myocardial infarction, with strong immunoreactivity in platelet aggregates. Our in vitro experiments identified a role for platelet-and endothelialderived DKK-1 in platelet-dependent endothelial activation, promoting enhanced release of inflammatory cytokines. These inflammatory effects of DKK-1 involved inhibition of the Wnt/␤-catenin pathway and activation of nuclear factor B. Key Words: atherosclerosis Ⅲ endothelium Ⅲ inflammation Ⅲ platelets P roteins from the wingless (Wnt) signaling pathways are involved in diverse developmental and physiological processes, including cardiac and vascular development. Wnt signals are transduced to the canonical and the noncanonical pathways for control of cell fate, cell movement, and tissue polarity. 1 The Wnt pathways are regulated by multiple families of secreted antagonists including soluble frizzled related receptors and dickkopfs (DKK). The best studied of these is DKK-1, which dampens Wnt signaling by binding to the low-density lipoprotein receptor-related protein (LRP)5/6 and a cell surface coreceptor, Kremen-1, promoting internalization of the receptor complex. 2 In adults, DKK-1 has been implicated in bone disease, cancer, and brain ischemia, and most recently, the destructive effect of tumor necrosis factor ␣ (TNF␣) on joints in rheumatoid arthritis was found to involve DKK-1. 2,3 Also, serum levels of DKK-1 give prognostic information in patients with multiple myeloma and other malignancies as well as in patients with osteoarthritis. 4,5 Recent evidence points to an important role of the Wnt signaling pathways in the regulation of inflammation. Thus, activation of the canonical Wnt/␤-catenin pathway induces proliferation and survival of endothelial cells, enhances monocyte adhesion, and regulates transendothelial migration of monocytes. 6 -9 Moreover, activation of the noncanonical pathway has been shown to regulate inflammatory responses of human monocytes and macrophages in vitro. 10,11 However, the interaction between the different proteins in the Wnt family is rather complex, and the role Conclusion-Our