Takashi Yoshida, Tetsutaro Nagaoka, Yuichi Nagata, Yoshifumi Suzuki, Takeo Tsutsumi, Sachiko Kuriyama, Junko Watanabe, Shinsaku Togo, Fumiyuki Takahashi, Masakazu Matsushita, Yusuke Joki, HakuohKonishi, Satoshi Nunomura, Kenji Izuhara, Simon J. Conway, Kazuhisa Takahashi
Juntendo University Faculty of Medicine and Graduate School of Medicine. Saga Medical School. Indiana University School of Medicine.
Japan and United States
Respirology
Respirology 2022; 27: 529-538
DOI: 10.1111/resp.14249
Abstract
Background and objective: Remodelling of pulmonary arteries (PA) contributes to the progression of pulmonary hypertension (PH). Periostin, a matricellular protein, has been reported to be involved in the development of PH. We examined the role of periostin in the pathogenesis of PH using different types of experimental PH.
Methods: PH was induced by vascular endothelial growth factor receptor antagonist (Sugen5416) plus hypoxic exposure (SuHx) and venous injection of monocrotaline-pyrrole (MCT-P) in wild-type (WT) and periostin-/- mice. Pulmonary haemodynamics, PA remodelling, expression of chemokines and fibroblast growth factor (FGF)-2, accumulation of macrophages to small PA and the right ventricle (RV) were examined in PH-induced WT and periostin-/- mice. Additionally, the role of periostin in the migration of macrophages, human PA smooth muscle (HPASMCs) and endothelial cells (HPMVECs) was investigated.
Results: In PH induced by SuHx and MCT-P, PH and accumulation of M2 macrophage to small PA were attenuated in periostin-/- mice. PA remodelling post-SuHx treatment was also mild in periostin-/- mice compared to WT mice. Expression of macrophage-associated chemokines and FGF-2 in lung tissue, and accumulation of CD68-positive cells in the RV were less in SuHx periostin-/- than in SuHx WT mice. Periostin secretion in HPASMCs and HPMVECs was enhanced by transforming growth factor-β. Periostin also augmented macrophage, HPASMCs and HPMVECs migration. Separately, serum periostin levels were significantly elevated in patients with PH compared to healthy controls.
Conclusion: Periostin is involved in the development of different types of experimental PH, and may also contribute to the pathogenesis of human PH.
Category
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Animal Models of Pulmonary Vascular Disease and Therapy
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes