Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026
The calcimimetic etelcalcetide attenuates pressure overload-induced cardiac hypertrophy in rats with and without chronic kidney disease.
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Okamoto Hidehisa, Goto Shunsuke, Nose Yuma, Okamoto Hayaki, Fujii Hideki
Аннотация
INTRODUCTION: Calcimimetics such as etelcalcetide (ET) are used to manage secondary hyperparathyroidism patients with chronic kidney disease (CKD) on dialysis. While their cardiovascular benefits-including left ventricular hypertrophy (LVH) suppression-are recognized, the underlying mechanisms remain unclear. This study investigated how ET suppresses LVH using rat models.
METHODS: LVH was induced via transverse aortic coarctation, and CKD by 5/6 nephrectomy. Rats were assigned to the sham, CKD, LVH, or CKD/LVH groups, with each pathological group further divided into vehicle- or ET-treated subgroups. After eight weeks of treatment, echocardiography, histological, biochemical, and molecular analyses were conducted.
RESULTS: ET reduced serum parathyroid hormone and fibroblast growth factor 23 (FGF23) levels in the CKD and CKD/LVH groups but not in the LVH group, where these levels were not increased. ET did not affect serum calcium, phosphorus, or vitamin D levels in the LVH and CKD/LVH groups. Nonetheless, ET suppressed cardiac hypertrophy and cardiomyocyte enlargement in the LVH and CKD/LVH groups despite no changes in systemic mineral metabolism parameters. Mechanistically, ET attenuated cardiac hypertrophy, serum aldosterone levels, and cardiac renin-angiotensin-aldosterone system (RAAS) components in the LVH and CKD/LVH groups. Cardiac FGF23 expression, elevated in the LVH and CKD/LVH groups, was also decreased by ET. The calcineurin/nuclear factor of the activated T-cell signaling pathway was unaffected.
CONCLUSION: ET effectively suppressed LVH in the LVH and CKD/LVH groups. These findings suggest that ET's cardioprotective effects are mediated via the modulation of the RAAS and cardiac FGF23 expression rather than solely through the correction of CKD-mineral bone disorder abnormalities.
METHODS: LVH was induced via transverse aortic coarctation, and CKD by 5/6 nephrectomy. Rats were assigned to the sham, CKD, LVH, or CKD/LVH groups, with each pathological group further divided into vehicle- or ET-treated subgroups. After eight weeks of treatment, echocardiography, histological, biochemical, and molecular analyses were conducted.
RESULTS: ET reduced serum parathyroid hormone and fibroblast growth factor 23 (FGF23) levels in the CKD and CKD/LVH groups but not in the LVH group, where these levels were not increased. ET did not affect serum calcium, phosphorus, or vitamin D levels in the LVH and CKD/LVH groups. Nonetheless, ET suppressed cardiac hypertrophy and cardiomyocyte enlargement in the LVH and CKD/LVH groups despite no changes in systemic mineral metabolism parameters. Mechanistically, ET attenuated cardiac hypertrophy, serum aldosterone levels, and cardiac renin-angiotensin-aldosterone system (RAAS) components in the LVH and CKD/LVH groups. Cardiac FGF23 expression, elevated in the LVH and CKD/LVH groups, was also decreased by ET. The calcineurin/nuclear factor of the activated T-cell signaling pathway was unaffected.
CONCLUSION: ET effectively suppressed LVH in the LVH and CKD/LVH groups. These findings suggest that ET's cardioprotective effects are mediated via the modulation of the RAAS and cardiac FGF23 expression rather than solely through the correction of CKD-mineral bone disorder abnormalities.