title: Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats.
abstract: Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of smooth muscle cells (SMCs), leading to occlusion of pulmonary arterioles, right ventricular (RV) hypertrophy, and death. We investigated whether mycophenolate mofetil (MMF), a potent immunosuppresssant, prevents the development of monocrotaline (MCT)-induced PAH in rats. MMF effectively decreased RV systolic pressure and RV hypertrophy, and reduced the medial thickness of pulmonary arteries. MMF significantly inhibited the number of proliferating cell nuclear antigen (PCNA)-positive cells, infiltration of macrophages, and expression of P-selectin and interleukin-6 on the endothelium of pulmonary arteries. The infiltration of T cells and mast cells was not affected by MMF. In vitro experiments revealed that mycophenolic acid (MPA), an active metabolite of MMF, dose-dependently inhibited proliferation of human pulmonary arterial SMCs. MMF attenuated the development of PAH through its anti-inflammatory and anti-proliferative properties. These findings provide new insight into the potential role of immunosuppressants in the treatment of PAH.
authors.affiliation: Division of Cardiovascular Sciences, Department of Organ Regeneration, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Suzuki
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takahashi
authors.forename: Hajime
authors.initials: H
authors.lastname: Morimoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Izawa
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Ise
authors.forename: Minoru
authors.initials: M
authors.lastname: Hongo
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hoshikawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyashita
authors.forename: Eiji
authors.initials: E
authors.lastname: Kobayashi
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Shimada
authors.forename: Uichi
authors.initials: U
authors.lastname: Ikeda
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D049109:Cell Proliferation; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D017380:Hypertrophy, Right Ventricular; D008264:Macrophages / Q000378:metabolism; D008297:Male; D016686:Monocrotaline / Q000378:metabolism; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016686:Monocrotaline; D009173:Mycophenolic Acid