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.

Astragaloside IV inhibits isoprenaline-induced cardiac fibrosis by targeting the reactive oxygen species/mitogen-activated protein kinase signaling axis

“…Oxidative stress is important in the development and progression of diverse cardiac disorders, including cardiac fibrosis (14), hypertrophy (22), apoptosis (23), inflammation (24) and resultant heart failure (25,26). It has previously been demonstrated that ROS may modulate ECM remodeling by mediating CF function and stimulating collagen turnover (26).…”

Fibroblast growth factor-21 prevents diabetic cardiomyopathy via AMPK-mediated antioxidation and lipid-lowering effects in the heart

“…CH of mice was evaluated by three methods 42 , 46 : (1) measurement of LV mass; (2) calculating the relative heart weight; and (3) detecting the changes of CH markers. See supplementary methods for details.…”

Pyrroloquinoline quinone attenuates isoproterenol hydrochloride‑induced cardiac hypertrophy in AC16 cells by inhibiting the NF‑κB signaling pathway

“…The inflammatory response is one of the research hotspots in the pathogenesis of cardiac hypertrophy (26). Previous studies have demonstrated that the activation of the NF-κB signaling pathway is closely associated with the inflammatory response, and it has been reported that NF-κB is involved in vascular remodeling, apoptosis and oxidative stress (27)(28)(29)(30). In addition, previous studies have confirmed that Iso can cause cardiac hypertrophy by activating the NF-κB signaling pathway, while the inhibition of NF-κB activation can counteract Iso-induced hypertrophy (7,31).…”