DOI: 10.1161/CIRCULATIONAHA.113.005296 1 The Hypoxic Response Contributes to Altered Gene Expression and Pre-Capillary Pulmonary Hypertension in Patients with Sickle Cell Disease Running title: Zhang et al.; Hypoxia, MAPK8 and Pulmonary Hypertension in SCD Xu Zhang, PhD 1 ; Wei Zhang, PhD 2,3 ; Shwu-Fan Ma, PhD 4 ; Ankit A. Desai, MD 5,6 ; Santosh Saraf, MD 1 ; Galina Miasniakova, MD 7 ; Adelina Sergueeva, MD 8 ; Tatiana Ammosova, PhD 9 ; Min Xu, PhD 9 ; Sergei Nekhai, PhD 9 ; Taimur Abbasi, MD 6 ; Nancy G. Casanova, MD 6 ; Martin H. Steinberg, MD 10 ; Clinton T. Baldwin, PhD 10 ; Paola Sebastiani, PhD 11 ; Josef T. Prchal, MD 12 ; Rick Kittles, PhD 2 ; Joe G. N. Garcia, MD 6,13* ; Roberto F. Machado, MD 6,13* ; Victor R. Gordeuk, MD 1* 1 Comprehensive Sickle Cell Center, Section of Hematology/Oncology, Dept of Medicine; 2 Institute of Human Genetics; 3 Dept of Pediatrics; 4 Section of Pulmonary/Critical Care, Dept of Medicine; 5 Section of Cardiology, Dept of Medicine; 6 Institute for Personalized Respiratory Medicine; 13 Section of Pulmonary, Critical Care & Sleep Medicine, Dept of Medicine, University of Illinois at Chicago, Chicago, IL; 7 Chuvash Republic Clinical Hospital 2, Cheboksary, Russia; 8 Cheboksary Children's Hospital, Cheboksary, Russia; 9 Center for Sickle Cell Disease, Howard University, Washington, DC; 10 Dept of Medicine, Boston University School of Medicine, Boston, MA; 11 Dept of Biostatistics, Boston University School of Public Health, Boston, MA; 12 Hematology Division, University of Utah, Salt Lake City, UT * Contributed equally as senior authors Address for Correspondence: Victor R. Gordeuk, MD University of Illinois at Chicago Suite 172, Clinical Sciences Building 820 South Wood St. Chicago, IL 60612-7236 Tel: 312-996-5680 Fax: 312-996-5984 E-mail: vgordeuk@uic.edu Journal Subject Code: Hypertension:[18] Pulmonary circulation and disease 1 Comprehensive Sickle Cell Ce nter, Section of Hematology/ Oncology, Dept t o o of f Me Me Medi di dici ci cine ne ne; ; ; 2 Institute of Human Genetics; 3 Dept of Pediatrics; 4 Section of Pulmonary/Critical Care, Dept of Medicine; 5 Section of Cardiology, Dept of Medicine; 6 Institute for Personalized Respiratory Me Me Medi di dici cine n n ; 13 13 Se Se S ction of Pulmonary, Critical l C C Car a a e & Sleep Medici cine ne ne, , Dept of Medicine, U Univ ver er rs s sity y o of f Il Illi ino n is is at Ch Chicag ago, o C Chi h cago go, , I IL IL; 7 Ch huv uvas a h Re Re epu p publ blic ic C Clini ica al l Hosp pit tal l 2, Ch Ch heb e oksary ry, Ru Ru Rus s ssia ia a; ; 8 8 8 Ch Ch Cheb eb e ok ok oksa sa sary ry y C C Chi hi hild ld l re re re ' n' n's s s Ho Ho os sp pital al al, , Ch Ch Cheb eb e ok ok oksa a ary ry ry, , , Ru Ru Russia ia a; ; ; 9 9 9 Ce Ce Cent nt nter er r f f for or r S S Sic ic ickl kl k e C C Cell Disease, H H How wa ar rd d U Un n niv v versit it i y, y, W W Wa ashi ing ng gton n, D D DC; C; 1 10 10 D De Dep p pt o of f M M Medi i ici in ne, , B Bo Bosto on n U Un n niv v versi ity y y Sc Sc Scho ho h ol o of Me Me M d d dic c cine ne, , B Bo Bost sto on on, , MA MA A; ; ; 11 11 De Dept pt o of f f Bi B o os osta tati ti ist st tic ics, s, , B B Bos osto ton n Un Un niv v ver ers s sity ty y S Sch ch ho oo ool of f f P Pu ub bl li ic He He Heal al alth th th, Bo Bo Bost st ston on on, , MA MA MA; 12 2 2 He He Hem ma mato tolo logy gy gy D D Div iv ivis is isio io ion n n, U U Uni ni nive ve vers rs sit it ity y y of of of U U Uta ta ah, h, h S S Sal alt t La La Lake ke ke C C Cit it ty, y y, U U UT T T * * Co Co Cont nt ntri ri ribu bu bute te ted d d eq eq equa ua uall ll lly y y as as as s s sen en enio io ior r r au au auth th thor or ors s s