title: Celecoxib prevents pressure overload-induced cardiac hypertrophy and dysfunction by inhibiting inflammation, apoptosis and oxidative stress.
abstract: To explore the effects of celecoxib on pressure overload-induced cardiac hypertrophy (CH), cardiac dysfunction and explore the possible protective mechanisms. We surgically created abdominal aortic constrictions (AAC) in rats to induce CH. Rats with CH symptoms at 4 weeks after surgery were treated with celecoxib [2 mg/100 g body-weight(BW)] daily for either 2 or 4 weeks. Survival rate, blood pressure and cardiac function were evaluated after celecoxib treatment. Animals were killed, and cardiac tissue was examined for morphological changes, cardiomyocyte apoptosis, fibrosis, inflammation and oxidative stress. Four weeks after AAC, rats had significantly higher systolic, diastolic and mean blood pressure, greater heart weight and enlarged cardiomyocytes, which were associated with cardiac dysfunction. Thus, the CH model was successfully established. Two weeks later, animals had impaired cardiac function and histopathological abnormalities including enlarged cardiomyocytes and cardiac fibrosis, which were exacerbated 2 weeks later. However, these pathological changes were remarkably prevented by the treatment of celecoxib, independent of preventing hypertension. Mechanistic studies revealed that celecoxib-induced cardiac protection against CH and cardiac dysfunction was due to inhibition of apoptosis via the murine double mimute 2/P53 pathway, inhibition of inflammation via the AKT/mTOR/NF-κB pathway and inhibition of oxidative stress via increases in nuclear factor E2-related factor-2-mediated gene expression of multiple antioxidants. Celecoxib suppresses pressure overload-induced CH by reducing apoptosis, inflammation and oxidative stress.
authors.affiliation: Ruian Center of the Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China.|School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Beijing Hui-Long-Guan Hospital, Peking University, Beijing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
authors.forename: Yingxia
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
authors.forename: Haisheng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Si
authors.affiliation: Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Su
authors.affiliation: Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Xin
authors.affiliation: Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xue
authors.affiliation: Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Hao
authors.affiliation: Ruian Center of the Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Lechu
authors.initials: L
authors.lastname: Yu
authors.affiliation: The Affiliated Wenling Hospital of Wenzhou Medial University, Wenling, Zhejiang, China.
authors.forename: Jinzhong
authors.initials: J
authors.lastname: Xu
authors.affiliation: Ruian Center of the Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China.|School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Yanlong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Xue
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology / Q000517:prevention & control*; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000068579:Celecoxib / Q000494:pharmacology* / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D008297:Male; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D020257:Ventricular Remodeling
chemical_list: D002316:Cardiotonic Agents; D052246:Cyclooxygenase 2 Inhibitors; D000068579:Celecoxib
keywords: apoptosis; cardiac hypertrophy; celecoxib; inflammation; oxidative stress; pressure overload