Pulmonary Hypertension
Drs. Mark Gladwin and Gregory Kato have long studied the mechanism and treatment of pulmonary hypertension in patients with SCD:
- Kato GJ, Steinberg MH, Gladwin MT. (2017). Intravascular hemolysis and the pathophysiology of sickle cell disease. J Clin Invest. 127(3):750-760. doi: 10.1172/JCI89741. Epub 2017 Mar 1. PMID: 28248201. PMCID: PMC5330745.
- Gladwin MT. (2016). Cardiovascular complications and risk of death in sickle-cell disease. Lancet. 387(10037):2565-74. doi: 10.1016/S0140-6736(16)00647-4. PMID: 27353687.
- Mehari A, Gladwin MT, Tian X, Machado RF, Kato GJ. (2012). Mortality in adults with sickle cell disease and pulmonary hypertension. JAMA. 307(12):1254-6. doi: 10.1001/jama.2012.358. PMID: 22453563. PMCID: PMC3511048.
Drs. Gladwin and Kato are now leading a national trial of a nitric oxide mimetic drug, riociguat, affects adults with SCD, in partnership with Bayer:
A Multi-Center Study of Riociguat in Patients With Sickle Cell Diseases.
Clinical Trials Identifier: NCT02633397.
Sponsor: Greg Kato, MD
Dr. Gregory Kato and his lab group study how free heme induces erythroblasts to secrete placenta growth factor, which promotes pulmonary hypertension.
- Wang X, Mendelsohn L, Rogers H, Leitman S, Raghavachari N, Yang Y, Yau YY, Tallack M, Perkins A, Taylor JG 6th, Noguchi CT, Kato GJ. (2014). Heme-bound iron activates placenta growth factor in erythroid cells via erythroid Krüppel-like factor. Blood. 124(6):946-54. PMID: 24916507. PMCID: PMC4126333. doi: 10.1182/blood-2013-11-539718. Epub 2014 Jun 10.
- Sundaram N, Tailor A, Mendelsohn L, Wansapura J, Wang X, Higashimoto T, Pauciulo MW, Gottliebson W, Kalra VK, Nichols WC, Kato GJ, Malik P. (2010). High levels of placenta growth factor in sickle cell disease promote pulmonary hypertension. Blood. 116(1):109-12. PMID: 20335221. PMCID: PMC2904575. doi: 10.1182/blood-2009-09-244830. Epub 2010 Mar 24.
Drs. Karin Potoka and Mark Gladwin study the effects of other nitric oxide mimetics on pulmonary hypertension in the sickle cell mouse.
- Potoka KP, Gladwin MT. (2015). Vasculopathy and pulmonary hypertension in sickle cell disease. Am J Physiol Lung Cell Mol Physiol. 308(4):L314-24. doi: 10.1152/ajplung.00252.2014. Epub 2014 Nov 14. PMID: 25398989. PMCID: PMC4329471.
Drs. Novelli, Isenberg, Gladwin, Zhang and Kato have found a genetic association for the thrombospondin-1 gene with a marker of pulmonary hypertension in SCD.
- Jacob SA, Novelli EM, Isenberg JS, Garret ME, Chu Y, Soldano K, Ataga KI, Telen MJ, Ashley-Koch A, Gladwin MT, Zhang Y, Kato GJ. (2017). Thrombospondin-1 gene polymorphism is associated with estimated pulmonary artery pressure in patients with sickle cell anemia. Am J Hematol. 92(3):E31-E34. doi: 10.1002/ajh.24635. Epub 2017 Feb 3. PMID: 28033687. PMCID: PMC5303556.