title: Carvacrol induces the apoptosis of pulmonary artery smooth muscle cells under hypoxia.
abstract: The abnormal apoptosis of pulmonary artery smooth muscle cells (PASMCs) is an important pathophysiological process in pulmonary vascular remodeling and pulmonary arterial hypertension (PAH). Carvacrol, an essential oil compound from oregano and thyme, has displayed antimicrobial, antitumor, and antioxidant properties. Although carvacrol has pro-apoptosis properties in tumor cells, the underlying mechanisms of carvacrol in PASMC apoptosis remain unclear. Thus, in this study, we aim to investigate the role of carvacrol in pulmonary vascular remodeling and PASMC apoptosis in hypoxia. Right Ventricular Hypertrophy Measurements and pulmonary pathomorphology data show that the ratio of the heart weight/tibia length (HW/TL), the right ventricle/left ventricle plus septum (RV/LV+S) and the medial width of the pulmonary artery increased in chronic hypoxia and were reversed by carvacrol treatment under hypoxia. Additionally, carvacrol inhibited PASMC viability, attenuated oxidative stress, induced mitochondria membrane depolarization, increased the percentage of apoptotic cells, suppressed Bcl-2 expression, decreased procaspase-3 expression, promoted caspase-3 activation, and inhibited the ERK1/2 and PI3K/Akt pathway. Taken together, these findings suggest that carvacrol attenuates the pulmonary vascular remodeling and promotes PASMC apoptosis by acting on, at least in part, the intrinsic apoptotic pathway. This process might provide us new insight into the development of hypoxic pulmonary hypertension.
authors.affiliation: Department of Physiology, Harbin Medical University-Daqing, Daqing 163319, China.
authors.forename: Qianlong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Harbin Medical University-Daqing, Daqing 163319, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Fan
authors.affiliation: Department of Physiology, Harbin Medical University-Daqing, Daqing 163319, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Physiology, Harbin Medical University-Daqing, Daqing 163319, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Physiology, Harbin Medical University-Daqing, Daqing 163319, China.
authors.forename: Ruxia
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, China.
authors.forename: Hanping
authors.initials: H
authors.lastname: Qi
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, China. Electronic address: honglisundr2014@126.com.
authors.forename: Hongli
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, China. Electronic address: rachelzql@sina.com.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000081007:Cymenes; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D039821:Monoterpenes / Q000494:pharmacology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D011651:Pulmonary Artery / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D053148:Caspase 3; D000081007:Cymenes; D004792:Enzyme Precursors; D039821:Monoterpenes; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; C073316:carvacrol
keywords: Apoptosis; Carvacrol; Hypoxia; Pulmonary arterial hypertension; Pulmonary artery smooth muscle cells; Pulmonary vascular remodeling