Key result
2,5-dimethylcelecoxib suppressed cardiac hypertrophy, cardiac fibrosis, and renal damage, and reduced urinary albumin excretion without altering blood pressure in hypertension model mice.
Why the study?
DM-celecoxib previously prevented cardiac remodeling likely through Wnt/beta-catenin inhibition, a pathway implicated in chronic kidney disease and heart failure, motivating investigation of its cardiac and renal effects in hypertensive mice.
Does 2,5-dimethylcelecoxib prevent cardiac remodeling and kidney injury in angiotensin II and high-salt-induced hypertension model mice?
Does 2,5-dimethylcelecoxib prevent cardiac remodeling and kidney injury in angiotensin II and high-salt-induced hypertension model mice?
DM-celecoxib prevents cardiac remodeling and kidney injury in a mouse model of hypertension, suggesting potential therapeutic benefits for hypertensive heart and kidney diseases via Wnt/β-catenin signaling suppression.
BACKGROUND: We reported that 2,5-dimethylcelecoxib (DM-celecoxib), a celecoxib derivative that is unable to inhibit cyclooxygenase-2, prevented cardiac remodeling induced by sarcomeric gene mutation, left ventricular pressure overload, or β-adrenergic receptor stimulation. This effect seemed to be mediated by the inhibition of the canonical Wnt/β-catenin signaling pathway, which has been suggested to play a key role in the development of chronic kidney disease and chronic heart failure. METHOD: We investigated the effect of DM-celecoxib on cardiac remodeling and kidney injury in hypertension model mice induced by angiotensin II infusion in the absence or presence of high-salt load. RESULTS: DM-celecoxib prevented cardiac remodeling and markedly reduced urinary albumin excretion without altering blood pressure in those mice. Moreover, DM-celecoxib prevented podocyte injury, glomerulosclerosis, and interstitial fibrosis in the kidney of mice loaded with angiotensin II and high-salt load. DM-celecoxib reduced the phosphorylation level of Akt and activated glycogen synthase kinase-3, which led to the suppression of the Wnt/β-catenin signal in the heart and kidney. DM-celecoxib also reduced the expression level of snail, a key transcription factor for the epithelial-mesenchymal transition and of which gene is a target of the Wnt/β-catenin signal. CONCLUSION: Results of the current study suggested that DM-celecoxib could be beneficial for patients with hypertensive heart and kidney diseases.
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Yamamoto et al. (2020) studied Hypertension (Angiotensin II and high-salt-induced). 2,5-dimethylcelecoxib (DMC) vs. Control (no DMC) was evaluated on Cardiac hypertrophy, cardiac fibrosis, and urinary albumin excretion. 2,5-dimethylcelecoxib suppressed cardiac hypertrophy, cardiac fibrosis, and renal damage, and reduced urinary albumin excretion without altering blood pressure in hypertension model mice.
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