Konstam MA, Notter T, et al. Longterm effects of darusentan on left-ventricular remodelling and clinical outcomes in the EndothelinA Receptor Madrasin site Antagonist Trial in Heart Failure: randomised, double-blind, placebo-controlled trial. Lancet 364: 347E354. 9. O’Connor CM, Gattis WA, Adams KF Jr, Hasselblad V, Chandler B, et al. Tezosentan in individuals with acute heart failure and acute coronary syndromes: benefits on the Randomized Intravenous TeZosentan Study. J Am Coll Cardiol 41: 14521457. 10. Kirkby NS, Hadoke PW, Bagnall AJ, Webb DJ The endothelin technique as a therapeutic target in cardiovascular disease: fantastic expectations or bleak property Br J Pharmacol 153: 11051119. 11. Vignon-Zellweger N, Relle K, Kienlen E, Alter M, Seider P, et al. Endothelin-1 overexpression restores diastolic function in eNOS knockout mice. J Hypertens 29: 961970. 12. Kakita T, Hasegawa K, Iwai-Kanai E, Adachi S, Morimoto T, et al. Calcineurin pathway is necessary for endothelin-1-mediated protection Licochalcone-A against oxidant stress-induced apoptosis in cardiac myocytes. Circ Res 88: 12391246. 13. Ogata Y, Takahashi M, Ueno S, Takeuchi K, Okada T, et al. Antiapoptotic impact of endothelin-1 in rat cardiomyocytes in vitro. Hypertension 41: 11561163. 14. Zhao XS, Pan W, Bekeredjian R, Shohet RV Endogenous endothelin-1 is necessary for cardiomyocyte survival in vivo. Circulation 114: 830837. 15. Kisanuki YY, Emoto N, Ohuchi T, Widyantoro B, Yagi K, et al. Low blood stress in endothelial cell-specific endothelin 1 knockout mice. Hypertension 56: 121128. 16. Shohet RV, Kisanuki YY, Zhao XS, Siddiquee Z, Franco F, et al. Mice with cardiomyocyte-specific disruption of the endothelin-1 gene are resistant to hyperthyroid cardiac hypertrophy. Proc Natl Acad Sci U S A 101: 20882093. 17. Widyantoro B, Emoto N, Nakayama K, Anggrahini DW, Adiarto S, et al. Endothelial cell-derived endothelin-1 promotes cardiac fibrosis in diabetic hearts by means of stimulation of endothelial-to-mesenchymal transition. Circulation 121: 24072418. 18. Polderman KH, Stehouwer CD, van Kamp GJ, Dekker GA, Verheugt FW, et al. Influence of sex hormones on plasma endothelin levels. Ann Intern Med 118: 429432. 19. Kedzierski RM, Grayburn PA, Kisanuki YY, Williams CS, Hammer RE, et al. Cardiomyocyte-specific endothelin A receptor knockout mice have 7 Endothelin-1 Is Expected for Typical Heart Function 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. normal cardiac function and an unaltered hypertrophic response to angiotensin II and isoproterenol. Mol Cell Biol 23: 82268232. Adiarto S, Heiden S, Vignon-Zellweger N, Nakayama K, Yagi K, et al. ET-1 from endothelial cells is expected for total angiotensin II-induced cardiac fibrosis and hypertrophy. Life Sci 91: 651657. Chen QM, Tu VC, Purdon S, Wood J, Dilley T Molecular mechanisms of cardiac hypertrophy induced by toxicants. Cardiovasc Toxicol 1: 267283. Fliegner D, Schubert C, Penkalla A, Witt H, Kararigas G, et al. Female sex and estrogen receptor-beta attenuate cardiac remodeling and apoptosis in stress overload. Am J Physiol Regul Integr Comp Physiol 298: R1597 R1606. Condorelli G, Morisco C, Stassi G, Notte A, Farina F, et al. Elevated Cardiomyocyte Apoptosis and Changes in Proapoptotic and Antiapoptotic Genes bax and bcl-2 During Left Ventricular Adaptations to Chronic Pressure Overload within the Rat. Circulation 99: 30713078. Moorjani N, Catarino P, Trabzuni D, Saleh S, Moorji A, et al. Upregulation of Bcl-2 proteins through the transition to pressure overl.Konstam MA, Notter T, et al. Longterm effects of darusentan on left-ventricular remodelling and clinical outcomes in the EndothelinA Receptor Antagonist Trial in Heart Failure: randomised, double-blind, placebo-controlled trial. Lancet 364: 347E354. 9. O’Connor CM, Gattis WA, Adams KF Jr, Hasselblad V, Chandler B, et al. Tezosentan in sufferers with acute heart failure and acute coronary syndromes: results on the Randomized Intravenous TeZosentan Study. J Am Coll Cardiol 41: 14521457. ten. Kirkby NS, Hadoke PW, Bagnall AJ, Webb DJ The endothelin system as a therapeutic target in cardiovascular disease: wonderful expectations or bleak house Br J Pharmacol 153: 11051119. 11. Vignon-Zellweger N, Relle K, Kienlen E, Alter M, Seider P, et al. Endothelin-1 overexpression restores diastolic function in eNOS knockout mice. J Hypertens 29: 961970. 12. Kakita T, Hasegawa K, Iwai-Kanai E, Adachi S, Morimoto T, et al. Calcineurin pathway is necessary for endothelin-1-mediated protection against oxidant stress-induced apoptosis in cardiac myocytes. Circ Res 88: 12391246. 13. Ogata Y, Takahashi M, Ueno S, Takeuchi K, Okada T, et al. Antiapoptotic effect of endothelin-1 in rat cardiomyocytes in vitro. Hypertension 41: 11561163. 14. Zhao XS, Pan W, Bekeredjian R, Shohet RV Endogenous endothelin-1 is necessary for cardiomyocyte survival in vivo. Circulation 114: 830837. 15. Kisanuki YY, Emoto N, Ohuchi T, Widyantoro B, Yagi K, et al. Low blood stress in endothelial cell-specific endothelin 1 knockout mice. Hypertension 56: 121128. 16. Shohet RV, Kisanuki YY, Zhao XS, Siddiquee Z, Franco F, et al. Mice with cardiomyocyte-specific disruption in the endothelin-1 gene are resistant to hyperthyroid cardiac hypertrophy. Proc Natl Acad Sci U S A 101: 20882093. 17. Widyantoro B, Emoto N, Nakayama K, Anggrahini DW, Adiarto S, et al. Endothelial cell-derived endothelin-1 promotes cardiac fibrosis in diabetic hearts by way of stimulation of endothelial-to-mesenchymal transition. Circulation 121: 24072418. 18. Polderman KH, Stehouwer CD, van Kamp GJ, Dekker GA, Verheugt FW, et al. Influence of sex hormones on plasma endothelin levels. Ann Intern Med 118: 429432. 19. Kedzierski RM, Grayburn PA, Kisanuki YY, Williams CS, Hammer RE, et al. Cardiomyocyte-specific endothelin A receptor knockout mice have 7 Endothelin-1 Is Required for Normal Heart Function 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. regular cardiac function and an unaltered hypertrophic response to angiotensin II and isoproterenol. Mol Cell Biol 23: 82268232. Adiarto S, Heiden S, Vignon-Zellweger N, Nakayama K, Yagi K, et al. ET-1 from endothelial cells is required for total angiotensin II-induced cardiac fibrosis and hypertrophy. Life Sci 91: 651657. Chen QM, Tu VC, Purdon S, Wood J, Dilley T Molecular mechanisms of cardiac hypertrophy induced by toxicants. Cardiovasc Toxicol 1: 267283. Fliegner D, Schubert C, Penkalla A, Witt H, Kararigas G, et al. Female sex and estrogen receptor-beta attenuate cardiac remodeling and apoptosis in pressure overload. Am J Physiol Regul Integr Comp Physiol 298: R1597 R1606. Condorelli G, Morisco C, Stassi G, Notte A, Farina F, et al. Elevated Cardiomyocyte Apoptosis and Modifications in Proapoptotic and Antiapoptotic Genes bax and bcl-2 In the course of Left Ventricular Adaptations to Chronic Stress Overload inside the Rat. Circulation 99: 30713078. Moorjani N, Catarino P, Trabzuni D, Saleh S, Moorji A, et al. Upregulation of Bcl-2 proteins during the transition to pressure overl.