Research Topics
| E D MichelakisSummaryAffiliation: University of Alberta Country: Canada Publications
| Collaborators
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Detail Information
Publications
Emerging concepts and translational priorities in pulmonary arterial hypertensionEvangelos D Michelakis
Department of Medicine, Cardiology Division, Pulmonary Hypertension Program, University of Alberta, Edmonton, Alberta, Canada
Circulation 118:1486-95. 2008
Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancerE D Michelakis
Department of Medicine, University of Alberta, Edmonton, Canada
Br J Cancer 99:989-94. 2008..Here, we review the scientific and clinical rationale supporting the rapid translation of this promising metabolic modulator in early-phase cancer clinical trials...- An evidence-based approach to the management of pulmonary arterial hypertensionStephen L Archer
Vascular Biology Group, Division of Cardiology, Canada
Curr Opin Cardiol 21:385-92. 2006..Evidence-based therapies and guidelines for pulmonary arterial hypertension are critiqued... - Dexfenfluramine elevates systemic blood pressure by inhibiting potassium currents in vascular smooth muscle cellsE D Michelakis
Department of Medicine Cardiology, Walter C Mackenzie Health Sciences Center, University of Alberta, Edmonton, Alberta, Canada
J Pharmacol Exp Ther 291:1143-9. 1999..To our knowledge, this is the first time that a commonly prescribed drug with voltage-gated K(+) channel-blocking properties is shown to have significant hemodynamic effects in vivo... - Potassium channels regulate tone in rat pulmonary veinsE D Michelakis
Department of Medicine Cardiology, University of Alberta, Edmonton, Alberta T6G 2B7, Canada
Am J Physiol Lung Cell Mol Physiol 280:L1138-47. 2001..We conclude that K(+) channels are present and functionally important in rat PVs. PVCMs form sphincters rich in K(ir) channels, which may modulate venous return both physiologically and in disease states including pulmonary edema... 
Metabolic modulation of glioblastoma with dichloroacetateE D Michelakis
Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
Sci Transl Med 2:31ra34. 2010..Metabolic modulation may be a viable therapeutic approach in the treatment of glioblastoma...- Anorectic drugs and pulmonary hypertension from the bedside to the benchE D Michelakis
Department of Medicine, University of Alberta, Edmonton, Canada
Am J Med Sci 321:292-9. 2001..One potentially beneficial effect of the epidemics of anorectic-related PPH is that it may have provided important insights into the causes of PPH unrelated to anorectic agents... - The pathobiology of pulmonary hypertension. Smooth muscle cells and ion channelsE D Michelakis
Department of Medicine, Division of Cardiology, the Vascular Biology Group, University of Alberta, Edmonton, Canada
Clin Chest Med 22:419-32. 2001..The selective Kv1.5 down-regulation leaves wide open the door to replacement gene therapy in pulmonary hypertension research... - Gene transfer and metabolic modulators as new therapies for pulmonary hypertension. Increasing expression and activity of potassium channels in rat and human modelsE D Michelakis
Department of Medicine (Cardiology, University of Alberta, Edmonton, Canada
Adv Exp Med Biol 502:401-18. 2001..Adenoviral gene transfer increased expression of Kv2.1 channels and enhanced 4-AP constriction in human PAs. CONCLUSION: Increasing Kv channel function in PAs is feasible and might be beneficial... - The role of k+ channels in determining pulmonary vascular tone, oxygen sensing, cell proliferation, and apoptosis: implications in hypoxic pulmonary vasoconstriction and pulmonary arterial hypertensionRohit Moudgil
Vascular Biology Group, Division of Cardiology, University of Alberta, Edmonton, Canada
Microcirculation 13:615-32. 2006..In conclusion, K+ channels regulate pulmonary vascular tone and remodeling and constitute potential therapeutic targets in the regression of PAH... - Overexpression of human bone morphogenetic protein receptor 2 does not ameliorate monocrotaline pulmonary arterial hypertensionM Sean McMurtry
Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2B7
Am J Physiol Lung Cell Mol Physiol 292:L872-8. 2007..Depressed BMPR2 expression may be a marker of PAH but is not central to the pathogenesis of this model of PAH... - A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growthSebastien Bonnet
Pulmonary Hypertension Program and Vascular Biology Group, Department of Physiology, University of Alberta, Edmonton, AB T6G 2B7, Canada
Cancer Cell 11:37-51. 2007..Molecular inhibition of PDK2 by siRNA mimics DCA. The mitochondria-NFAT-Kv axis and PDK are important therapeutic targets in cancer; the orally available DCA is a promising selective anticancer agent... - The nuclear factor of activated T cells in pulmonary arterial hypertension can be therapeutically targetedSebastien Bonnet
Pulmonary Hypertension Program, University of Alberta, Edmonton, AB, Canada IGG 2B7
Proc Natl Acad Sci U S A 104:11418-23. 2007..The generalized activation of NFAT in human and experimental PAH might regulate the ionic, mitochondrial, and inflammatory remodeling and be a therapeutic target and biomarker... - Statin therapy, alone or with rapamycin, does not reverse monocrotaline pulmonary arterial hypertension: the rapamcyin-atorvastatin-simvastatin studyM Sean McMurtry
Vascular Biology Group, University of Alberta, Edmonton, Ontario, Canada
Am J Physiol Lung Cell Mol Physiol 293:L933-40. 2007..These negative results should be considered as human trials with these agents are underway (simvastatin) or proposed (rapamycin)... - The metabolic basis of vascular oxygen sensing: diversity, compartmentalization, and lessons from cancerEvangelos D Michelakis
Am J Physiol Heart Circ Physiol 295:H928-H930. 2008 - An abnormal mitochondrial-hypoxia inducible factor-1alpha-Kv channel pathway disrupts oxygen sensing and triggers pulmonary arterial hypertension in fawn hooded rats: similarities to human pulmonary arterial hypertensionSebastien Bonnet
Vascular Biology Group, Division of Cardiology, University of Alberta, Edmonton, Canada
Circulation 113:2630-41. 2006..The cause of pulmonary arterial hypertension (PAH) was investigated in humans and fawn hooded rats (FHR), a spontaneously pulmonary hypertensive strain... - Spatio-temporal diversity of apoptosis within the vascular wall in pulmonary arterial hypertension: heterogeneous BMP signaling may have therapeutic implicationsEvangelos D Michelakis
Circ Res 98:172-5. 2006 - The role of the NO axis and its therapeutic implications in pulmonary arterial hypertensionEvangelos D Michelakis
University of Alberta Hospitals, Walter C McKenzie Health Sciences Centre, Edmonton, Canada
Heart Fail Rev 8:5-21. 2003..It focuses on the role of recent therapies that target the NO pathway, including L-Arginine, inhaled NO, the phosphodiesterase inhibitor sildenafil and gene therapy... - In vivo gene transfer of the O2-sensitive potassium channel Kv1.5 reduces pulmonary hypertension and restores hypoxic pulmonary vasoconstriction in chronically hypoxic ratsZlatko I Pozeg
Vascular Biology Group, Cardiology, University of Alberta, Edmonton, Canada
Circulation 107:2037-44. 2003..5 is an important O2-sensitive channel and potential therapeutic target in PHT. Kv1.5 gene therapy restores HPV and improves PHT. This is, to the best of our knowledge, the first example of K+ channel gene therapy for a vascular disease... - Long-term treatment with oral sildenafil is safe and improves functional capacity and hemodynamics in patients with pulmonary arterial hypertensionEvangelos D Michelakis
Vascular Biology Group and Pulmonary Hypertension Program, Department of Medicine, University of Alberta, 2C2 Walter C Mackenzie Health Sciences Centre, 8440 112th St, Edmonton, Alberta, Canada, T6G 2B7
Circulation 108:2066-9. 2003..However, the long-term effects of PD-5 inhibition and its mechanism of action in human pulmonary arteries (PAs) are unknown... - The NO - K+ channel axis in pulmonary arterial hypertension. Activation by experimental oral therapiesEvangelos D Michelakis
University of Alberta Hospitals, 2C2 Walker C McKenzie Health Sciences, Centre, Edmonton, Canada
Adv Exp Med Biol 543:293-322. 2003..These drugs appear safe in humans and may be useful PAH therapies, alone or in combination... - Dichloroacetate prevents and reverses pulmonary hypertension by inducing pulmonary artery smooth muscle cell apoptosisM Sean McMurtry
Department of Medicine and Pediatrics, University of Alberta, Edmonton, Canada
Circ Res 95:830-40. 2004..5 in the media. We identify mitochondria-dependent apoptosis as a potential target for therapy and DCA as an effective and selective treatment for PAH... - Hypoxic pulmonary vasoconstrictionRohit Moudgil
Cardiology Division, Dept. of Medicine, and Vascular Biology Group, University of Alberta, WMC 2C2.36, 8440 112th Street, Edmonton, Alberta, Canada T6G 2B7
J Appl Physiol 98:390-403. 2005..HPV is clinically exploited in single-lung anesthesia, and its mechanisms intersect with those of pulmonary arterial hypertension... - Gene therapy targeting survivin selectively induces pulmonary vascular apoptosis and reverses pulmonary arterial hypertensionM Sean McMurtry
The Vascular Biology Group and Pulmonary Hypertension Program, University of Alberta, Edmonton, Alberta, Canada
J Clin Invest 115:1479-91. 2005..Inhibition of the inappropriate expression of survivin that accompanies human and experimental PAH is a novel therapeutic strategy that acts by inducing vascular mitochondria-dependent apoptosis... - Dichloroacetate, a metabolic modulator, prevents and reverses chronic hypoxic pulmonary hypertension in rats: role of increased expression and activity of voltage-gated potassium channelsEvangelos D Michelakis
Department of Medicine, University of Alberta, Edmonton, Canada
Circulation 105:244-50. 2002..We hypothesized that dichloroacetate (DCA), a metabolic modulator that can shift redox balance toward an oxidized state and increase Kv current in myocardial cells, would reverse CH-PHT... - Vascular endothelial growth factor gene therapy increases survival, promotes lung angiogenesis, and prevents alveolar damage in hyperoxia-induced lung injury: evidence that angiogenesis participates in alveolarizationBernard Thebaud
Division of Neonatology, Department of Pediatrics, University of Alberta, Edmonton, Canada
Circulation 112:2477-86. 2005..Vascular endothelial growth factor (VEGF) is a trophic factor required for endothelial cell survival and is abundantly expressed in the lung...