BACKGROUND AND OBJECTIVES: Endothelin-1 has been associated with development of hypoxia-related pulmonary hypertension and vascular endothelial growth factor (VEGF) with protection from this complication. In Chuvash polycythemia, homozygous germline von Hippel-Lindau (VHL) 598C->T leads to up-regulation during normoxia of hypoxia inducible factor-1a and several hypoxia-controlled genes including erythropoietin and VEGF. We postulated that endothelin-1 and pulmonary artery pressure may be elevated in Chuvash polycythemia. DESIGN AND METHODS: Systolic pulmonary artery blood pressure was estimated by Doppler echocardiography and plasma concentrations of endothelin-1, VEGF and erythropoietin were determined in 14 patients with Chuvash polycythemia and 14 controls. Results. Plasma endothelin-1 (p=0.010), VEGF (p=0.022) and erythropoietin (p<0.0005) concentrations and Doppler-estimated systolic pulmonary artery pressures (p<0.0005) were higher in the patients while systolic systemic blood pressures were lower (p=0.001). Five (36%) patients and no controls had mild pulmonary hypertension defined as systolic pulmonary artery pressure (c) 35 mmHg. Among the patients with Chuvash polycythemia, the trends of association of estimated pulmonary artery pressure with plasma concentrations of endothelin-1 (R = +0.236), VEGF (R = -0.389) and erythropoietin (R = +0.220) were not statistically significant. INTERPRETATIONS AND CONCLUSIONS: Estimated systolic pulmonary artery pressure and plasma concentrations of endothelin-1 and VEGF are increased in patients with Chuvash polycythemia patients. The lack of significant associations of estimated systolic pulmonary artery pressure with plasma endothelin-1 and VEGF levels could conceivably be due to the small sample size. Further studies are indicated, especially in view of the reported efficacy of endothelin-1 receptor blockers in treating hypoxia-associated pulmonary hypertension.
BACKGROUND AND OBJECTIVES:Endothelin-1 has been associated with development of hypoxia-related pulmonary hypertension and vascular endothelial growth factor (VEGF) with protection from this complication. In Chuvash polycythemia, homozygous germline von Hippel-Lindau (VHL) 598C->T leads to up-regulation during normoxia of hypoxia inducible factor-1a and several hypoxia-controlled genes including erythropoietin and VEGF. We postulated that endothelin-1 and pulmonary artery pressure may be elevated in Chuvash polycythemia. DESIGN AND METHODS: Systolic pulmonary artery blood pressure was estimated by Doppler echocardiography and plasma concentrations of endothelin-1, VEGF and erythropoietin were determined in 14 patients with Chuvash polycythemia and 14 controls. Results. Plasma endothelin-1 (p=0.010), VEGF (p=0.022) and erythropoietin (p<0.0005) concentrations and Doppler-estimated systolic pulmonary artery pressures (p<0.0005) were higher in the patients while systolic systemic blood pressures were lower (p=0.001). Five (36%) patients and no controls had mild pulmonary hypertension defined as systolic pulmonary artery pressure (c) 35 mmHg. Among the patients with Chuvash polycythemia, the trends of association of estimated pulmonary artery pressure with plasma concentrations of endothelin-1 (R = +0.236), VEGF (R = -0.389) and erythropoietin (R = +0.220) were not statistically significant. INTERPRETATIONS AND CONCLUSIONS: Estimated systolic pulmonary artery pressure and plasma concentrations of endothelin-1 and VEGF are increased in patients with Chuvash polycythemiapatients. The lack of significant associations of estimated systolic pulmonary artery pressure with plasma endothelin-1 and VEGF levels could conceivably be due to the small sample size. Further studies are indicated, especially in view of the reported efficacy of endothelin-1 receptor blockers in treating hypoxia-associated pulmonary hypertension.
Authors: Cynthia M Beall; Gianpiero L Cavalleri; Libin Deng; Robert C Elston; Yang Gao; Jo Knight; Chaohua Li; Jiang Chuan Li; Yu Liang; Mark McCormack; Hugh E Montgomery; Hao Pan; Peter A Robbins; Kevin V Shianna; Siu Cheung Tam; Ngodrop Tsering; Krishna R Veeramah; Wei Wang; Puchung Wangdui; Michael E Weale; Yaomin Xu; Zhe Xu; Ling Yang; M Justin Zaman; Changqing Zeng; Li Zhang; Xianglong Zhang; Pingcuo Zhaxi; Yong Tang Zheng Journal: Proc Natl Acad Sci U S A Date: 2010-06-07 Impact factor: 11.205
Authors: Joe G N Garcia; Roberto F Machado; Victor R Gordeuk; Xu Zhang; Wei Zhang; Shwu-Fan Ma; Galina Miasniakova; Adelina Sergueeva; Tatiana Ammosova; Min Xu; Sergei Nekhai; Mehdi Nourai; Michael S Wade; Josef T Prchal Journal: Blood Cells Mol Dis Date: 2013-08-28 Impact factor: 3.039
Authors: Patrick R Arsenault; Fei Pei; Rebecca Lee; Heddy Kerestes; Melanie J Percy; Brian Keith; M Celeste Simon; Terence R J Lappin; Tejvir S Khurana; Frank S Lee Journal: J Biol Chem Date: 2013-10-11 Impact factor: 5.157
Authors: Michele M Hickey; Jennifer C Lam; Natalie A Bezman; W Kimryn Rathmell; M Celeste Simon Journal: J Clin Invest Date: 2007-12 Impact factor: 14.808