title: Erythropoietin, but not asialoerythropoietin or carbamyl-erythropoietin, attenuates monocrotaline-induced pulmonary hypertension in rats.
abstract: Erythropoietin (EPO) has long been utilized for the treatment of renal anemia. The erythropoietin receptor (EPOR) is also expressed in the cardiovascular and central nervous systems in addition to an erythroid lineage, to provide an organoprotective role against several types of cellular stress. Pulmonary hypertension (PH) is a poor prognostic disease caused by primary and secondary pulmonary vascular injury. We observed the effects of EPO derivatives on monocrotaline-induced PH in rats on the supposition that EPO may protect small arteries from injury. Asialoerythropoietin (AEPO) lacks sialic acids in the termini of carbohydrate chains that results in rapid clearance from blood. Carbamyl-erythropoietin (CEPO) interacts with EPOR/βc heterodimers, but not with EPOR homodimers expressed in erythroid cells. Monocrotaline-injected rats were treated with continuous intravenous injection of 2500 ng/kg/day of EPO, AEPO, or CEPO for 21 days, and lung histology, cardiac function, and mRNA expression in the lungs were examined. Wall thickening of small arteries in the lungs and PH were improved by administration of EPO, but not by its non-hematopoietic derivatives, AEPO, or CEPO. Erythropoietin administration increased mRNA expression of the anti-apoptotic molecule, Bcl-xL, and maintained expression of the CD31 antigen. We conclude that lungs may express EPOR homoreceptors, but not heteroreceptors. Adequate serum erythropoietin levels may be essential for pulmonary protective effects.
authors.affiliation: Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Ikarashi
authors.forename: Ken
authors.initials: K
authors.lastname: Toba
authors.forename: Kiminori
authors.initials: K
authors.lastname: Kato
authors.forename: Takuya
authors.initials: T
authors.lastname: Ozawa
authors.forename: Masato
authors.initials: M
authors.lastname: Oda
authors.forename: Tsugumi
authors.initials: T
authors.lastname: Takayama
authors.forename: Hironori
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Takao
authors.initials: T
authors.lastname: Yanagawa
authors.forename: Haruo
authors.initials: H
authors.lastname: Hanawa
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Suzuki
authors.forename: Mikio
authors.initials: M
authors.lastname: Nakazawa
authors.forename: Minoru
authors.initials: M
authors.lastname: Nomoto
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Asami
authors.forename: Masato
authors.initials: M
authors.lastname: Higuchi
authors.forename: Hideki
authors.initials: H
authors.lastname: Saito
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
mesh_terms: D000818:Animals; D001212:Asialoglycoproteins / Q000494:pharmacology; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008297:Male; D016686:Monocrotaline; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017467:Receptors, Erythropoietin / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D001212:Asialoglycoproteins; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; C500605:asialoerythropoietin; C488171:carbamylated erythropoietin; D004921:Erythropoietin; D016686:Monocrotaline