title: Thymosin Beta 4 protects mice from monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy.
abstract: Pulmonary hypertension (PH) is a progressive vascular disease of pulmonary arteries that impedes ejection of blood by the right ventricle. As a result there is an increase in pulmonary vascular resistance and pulmonary arterial pressure causing right ventricular hypertrophy (RVH) and RV failure. The pathology of PAH involves vascular cell remodeling including pulmonary arterial endothelial cell (PAEC) dysfunction and pulmonary arterial smooth muscle cell (PASMC) proliferation. Current therapies are limited to reverse the vascular remodeling. Investigating a key molecule is required for development of new therapeutic intervention. Thymosin beta-4 (Tβ4) is a ubiquitous G-actin sequestering protein with diverse biological function and promotes wound healing and modulates inflammatory responses. However, it remains unknown whether Tβ4 has any protective role in PH. The purpose of this study is to evaluate the whether Tβ4 can be used as a vascular-protective agent. In monocrotaline (MCT)-induced PH mouse model, we showed that mice treated with Tβ4 significantly attenuated the systolic pressure and RVH, compared to the MCT treated mice. Our data revealed for the first time that Tβ4 selectively targets Notch3-Col 3A-CTGF gene axis in preventing MCT-induced PH and RVH. Our study may provide pre-clinical evidence for Tβ4 and may consider as vasculo-protective agent for the treatment of PH induced RVH.
authors.affiliation: Division of Molecular Cardiology, Department of Medicine, College of Medicine, Texas A & M Health Science Center and Scott & White, Central Texas Veterans Health Care System, Temple, Texas, United States of America.
authors.forename: Chuanyu
authors.initials: C
authors.lastname: Wei
authors.affiliation: Division of Molecular Cardiology, Department of Medicine, College of Medicine, Texas A & M Health Science Center and Scott & White, Central Texas Veterans Health Care System, Temple, Texas, United States of America.
authors.forename: Il-Kwon
authors.initials: IK
authors.lastname: Kim
authors.affiliation: Division of Molecular Cardiology, Department of Medicine, College of Medicine, Texas A & M Health Science Center and Scott & White, Central Texas Veterans Health Care System, Temple, Texas, United States of America; Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China.
authors.forename: Liling
authors.initials: L
authors.lastname: Wu
authors.affiliation: Division of Molecular Cardiology, Department of Medicine, College of Medicine, Texas A & M Health Science Center and Scott & White, Central Texas Veterans Health Care System, Temple, Texas, United States of America.
authors.forename: Sudhiranjan
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007274:Injections, Intraperitoneal; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D016686:Monocrotaline / Q000633:toxicity*; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013947:Thymosin / Q000008:administration & dosage* / Q000494:pharmacology; D000099201:Thymosin beta(4)
chemical_list: D024061:Collagen Type III; D055513:Connective Tissue Growth Factor; D016686:Monocrotaline; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D013947:Thymosin; D000099201:Thymosin beta(4); C526318:CCN2 protein, mouse; C499373:Notch3 protein, mouse