Serum Klotho (but not haplotypes) associate with the post-myocardial infarction status of older adults

Paula, Roberta; Souza, Vinícius Carolino; Machado-Silva, Wilcelly; Almeida, Bruno Ratier S.; Daros, Andersen C.; Gomes, Lucy; Ferreira, Aparecido Pimentel; Brito, Ciro José; Córdova, Cláudio; Moraes, Clayton Franco; Nóbrega, Otávio de Tolêdo

doi:10.6061/clinics/2016(12)09

Cited by 12 publications

(11 citation statements)

References 57 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is possible that an increase in serum Klotho level at middle age could be a compensatory response to the increased aortic stiffness with age to maintain endothelium function and arterial compliance of peripheral arterial system. Similar adaptive mechanism has been proposed by Paula et al (2016) who observed an augmented level of Klotho in patients with myocardial infarction to ameliorate cardiac hypertrophy and remodeling. To the best of our knowledge, this study is the first to measure circulating Klotho concentrations with aging in swine, where species variations could be a potential factor that accounts for the different response of Klotho to advancing age between human and swine.…”

supporting

confidence: 77%

Increased Serum Klotho With Age-Related Aortic Stiffness and Peripheral Vascular Resistance in Young and Middle-Aged Swine

Guo

Kassab

2020

Front. Physiol.

View full text Add to dashboard Cite

The anti-aging function of Klotho gene has been implicated in age-related diseases. The physiological importance of Klotho in the progression of arterial stiffness with aging, however, remains unclear. The goal of this study is to determine the correlation of circulating Klotho with early age-related aortic stiffening and peripheral hemodynamics. We measured serum Klotho levels in a group of pigs with age ranges of 1.5-9 years and investigated the relationship between Klotho levels and biomarkers of aortic stiffening with aging, including aortic pulse wave velocity (PWV), augmentation index (AIx), and pulse pressure (PP). The effects of aortic stiffening on peripheral vascular resistance, compliance, and function were also evaluated. We found that increased aortic stiffness occurred at middle age (>5 years old), as evidenced by an increase in PWV and AIx (p < 0.001), but with no changes in blood pressure and PP. With advancing age, increased femoral vascular resistance positively correlated with aortic PWV and AIx (p < 0.01). No significant difference in endothelium function and arterial compliance for femoral and small peripheral arteries was observed between young and middle-aged groups. The serum Klotho levels were lower in young and higher in middle-aged pigs (p < 0.001), and a positive correlation was found between Klotho and aortic PWV, AIx, and femoral vascular resistance (p < 0.01). Our findings suggest that early-aged aortic stiffening has adverse effect on peripheral hemodynamics, independent of blood pressure levels. Elevated Klotho secretion was associated with increased aortic stiffness and peripheral vascular resistance with aging.

show abstract

supporting

confidence: 77%

Increased Serum Klotho With Age-Related Aortic Stiffness and Peripheral Vascular Resistance in Young and Middle-Aged Swine

Guo

Kassab

2020

Front. Physiol.

View full text Add to dashboard Cite

show abstract

“…In favor of a rationale that supports the compensatory action of Klotho, an association between serum Klotho level and classic risk factors, as well as a clinical history of cardiovascular diseases, has also been investigated. The examination group included 168 older adults with the prior coronary artery disease, myocardial infarction, and stroke [116]. Surprisingly, there was higher concentration of serum Klotho in patients with myocardial infarction in the past.…”

Section: Klotho Protein In Cardiac Hypertrophy and Remodelingmentioning

confidence: 99%

“…Surprisingly, there was higher concentration of serum Klotho in patients with myocardial infarction in the past. It suggests the compensatory mechanism of Klotho to prevent the development of pathological heart hypertrophy due to the cardiac damage [116]. Interestingly, the compensatory production of Klotho and thus renoprotection has not been noticeable in renal dysfunctions.…”

Section: Klotho Protein In Cardiac Hypertrophy and Remodelingmentioning

confidence: 99%

The Biological Role of Klotho Protein in the Development of Cardiovascular Diseases

Olejnik

Franczak

Krzywonos‐Zawadzka

et al. 2018

BioMed Research International

View full text Add to dashboard Cite

Klotho is a membrane-bound or soluble antiaging protein, whose protective activity is essential for a proper function of many organs. In 1997, an accidental insertion of a transgene led to creation of transgenic mice with several age-related disorders. In Klotho-deficient mice, the inherited phenotypes closely resemble human aging, while in an animal model of Klotho overexpression, the lifespan is extended. Klotho protein is detected mainly in the kidneys and brain. It is a coreceptor for fibroblast growth factor and hence is involved in maintaining endocrine system homeostasis. Furthermore, an inhibition of insulin/insulin-like growth factor-1 signaling pathway by Klotho regulates oxidative stress and reduces cell death. The association between serum Klotho and the classic risk factors, as well as the clinical history of cardiovascular disease, was also shown. There are a lot of evidences that Klotho deficiency correlates with the occurrence and development of coronary artery disease, atherosclerosis, myocardial infarction, and left ventricular hypertrophy. Therefore, an involvement of Klotho in the signaling pathways and in regulation of a proper cell metabolism could be a crucial factor in the cardiac and vascular protection. It is also well established that Klotho protein enhances the antioxidative response via augmented production of superoxide dismutase and reduced generation of reactive oxygen species. Recent studies have proven an expression of Klotho in cardiomyocytes and its increased expression in stress-related heart injury. Thus, the antioxidative and antiapoptotic activity of Klotho could be considered as the novel protective factor in cardiovascular disease and heart injury.

show abstract

“…Preincubation of adult rat ventricular cardiomyocytes with sKlotho also prevents FGF23‐induced pro‐arrhythmogenic effects [140]. Interestingly, patients who survive an MI have higher serum Klotho concentrations, possibly as a compensatory mechanism to prevent cardiac damage [141]. Finally, Klotho reduced the CKD‐associated left ventricular hypertrophy induced by administration of the uremic toxin indoxyl sulfate [142].…”

Section: Potential Roles Of Tweak–fn14 In the Mechanisms Linking Hearmentioning

confidence: 99%

TWEAK–Fn14 as a common pathway in the heart and the kidneys in cardiorenal syndrome

et al. 2021

View full text Add to dashboard Cite

There is a complex relationship between cardiac and renal disease, often referred to as the cardiorenal syndrome. Heart failure adversely affects kidney function, and both acute and chronic kidney disease are associated with structural and functional changes to the myocardium. The pathological mechanisms and contributing interactions that surround this relationship remain poorly understood, limiting the opportunities for therapeutic intervention. The cytokine tumor necrosis factor‐like weak inducer of apoptosis (TWEAK) and its receptor, fibroblast growth factor‐inducible 14 (Fn14), are abundantly expressed in injured kidneys and heart. The TWEAK–Fn14 axis promotes responses that drive tissue injury such as inflammation, proliferation, fibrosis, and apoptosis, while restraining the expression of tissue protective factors such as the anti‐aging factor Klotho and the master regulator of mitochondrial biogenesis peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α). High levels of TWEAK induce cardiac remodeling, and promote inflammation, tubular and podocyte injury and death, fibroblast proliferation, and, ultimately, renal fibrosis. Accordingly, targeting the TWEAK–Fn14 axis is protective in experimental kidney and heart disease. TWEAK has also emerged as a biomarker of kidney damage and cardiovascular outcomes and has been successfully targeted in clinical trials. In this review, we update our current knowledge of the roles of the TWEAK–Fn14 axis in cardiovascular and kidney disease and its potential contribution to the cardiorenal syndrome. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

show abstract

Serum Klotho (but not haplotypes) associate with the post-myocardial infarction status of older adults

Cited by 12 publications

References 57 publications

Increased Serum Klotho With Age-Related Aortic Stiffness and Peripheral Vascular Resistance in Young and Middle-Aged Swine

Increased Serum Klotho With Age-Related Aortic Stiffness and Peripheral Vascular Resistance in Young and Middle-Aged Swine

The Biological Role of Klotho Protein in the Development of Cardiovascular Diseases

TWEAK–Fn14 as a common pathway in the heart and the kidneys in cardiorenal syndrome

Contact Info

Product

Resources

About