2015
DOI: 10.1681/asn.2014040325
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Soluble Klotho Protects against Uremic Cardiomyopathy Independently of Fibroblast Growth Factor 23 and Phosphate

Abstract: Cardiac hypertrophy occurs in up to 95% of patients with CKD and increases their risk for cardiovascular death. In the kidney, full-length membranous Klotho forms the coreceptor for fibroblast growth factor 23 (FGF23) to regulate phosphate metabolism. The prevailing view is that the decreased level of Klotho in CKD causes cardiomyopathy through increases in serum FGF23 and/or phosphate levels. However, we reported recently that soluble Klotho protects against cardiac hypertrophy by inhibiting abnormal calcium … Show more

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Cited by 235 publications
(232 citation statements)
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“…With regard to cardiovascular dysfunction, Xie et al (133) showed that soluble Klotho protects the heart against stress-induced cardiac hypertrophy by inhibiting abnormal calcium signaling. Additional studies showed that intravenous delivery of a transgene coding for soluble Klotho protects against cardiomyopathy in Klotho-deficient CKD mice in a manner independent of FGF23 or phosphate (134). Intraperitoneal administration of Klotho protein to Klotho-deficient mice extended lifespan and attenuated systemic calcification and renal fibrosis; the protective effect on renal function was via downregulation of renal TGF-b mRNA expression, a main regulator of renal fibrosis (135).…”
Section: Indirect Approachesmentioning
confidence: 99%
“…With regard to cardiovascular dysfunction, Xie et al (133) showed that soluble Klotho protects the heart against stress-induced cardiac hypertrophy by inhibiting abnormal calcium signaling. Additional studies showed that intravenous delivery of a transgene coding for soluble Klotho protects against cardiomyopathy in Klotho-deficient CKD mice in a manner independent of FGF23 or phosphate (134). Intraperitoneal administration of Klotho protein to Klotho-deficient mice extended lifespan and attenuated systemic calcification and renal fibrosis; the protective effect on renal function was via downregulation of renal TGF-b mRNA expression, a main regulator of renal fibrosis (135).…”
Section: Indirect Approachesmentioning
confidence: 99%
“…Some would say this association between low eGFR and a higher risk of death "from a broken heart" is already well appreciated by the nephrology community. 4 As might be expected, in the Alberta study, after adjustment for age and sex, 33% of deaths were attributed to cardiovascular disease when the eGFR was 45-59 ml/min per 1.73 m 2 , and 40% of deaths were attributed to cardiovascular disease when the eGFR was 15-29 ml/min per 1.73 m 2 . 3 Similarly, in the Ohio study, the 3-year probability of mortality from cardiovascular disease increased in a graded manner as eGFR declined (from approximately 3% when the eGFR was 60 ml/min per 1.73 m 2 to 7.5% when the eGFR was 10 ml/min per 1.73 m 2 ).…”
Section: Disclosuresmentioning
confidence: 60%
“…12 However, recent studies show that normalization of serum phosphate and FGF-23 levels fails to abrogate cardiac hypertrophy in Klotho-deficient CKD mice, suggesting that Klotho prevents uremic cardiomyopathy by a mechanism independent of FGF-23 and phosphate. 4 These observations together with the study by Yang et al 6 underscore that the cardioprotection of Klotho is most likely mediated by its direct action on cardiomyocytes. Indeed, although the molecular details remain to be delineated, Klotho was shown to prevent IS-induced, ROS-mediated MAPK activation and cell hypertrophy in cultured cardiac myocytes.…”
mentioning
confidence: 89%
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“…Коррекция уровня фосфатов и витамина D предотвращает преждевременное старение, что является одним из воз-можных механизмов геропротекторного действия Klotho (Bian et al, 2015). Имеются данные о том, что повышение активности Klotho с помощью генной терапии увеличи-вает продолжительность жизни и улучшает показатели здоровья у животных с нехваткой Klotho (Wang, Sun, 2014;Xie et al, 2015).…”
Section: регуляция стресс-ответаunclassified