Klotho Protein and Cardio-Vascular System

Tyurenkov, I. N.; Перфилова, В. Н.; Nesterova, A. A.; Glinka, Yelena

doi:10.1134/s0006297921020024

Cited by 23 publications

(25 citation statements)

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“…In addition, the cardioprotective function of Klotho has also been attributed to its anti-apoptosis and pro-survival activities on endothelial cells and cardiomyocytes ( 37 ). Numerous studies have substantially enhanced our knowledge of Klotho’s antioxidative activity and its association with endothelial function ( 38 ). Klotho has been shown to regulate oxidative stress, fibrosis, and inflammation through suppression of insulin/insulin-like growth factor-1 and transforming growth factor-β1 signaling pathways ( 4 , 38 – 40 ).…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have substantially enhanced our knowledge of Klotho’s antioxidative activity and its association with endothelial function ( 38 ). Klotho has been shown to regulate oxidative stress, fibrosis, and inflammation through suppression of insulin/insulin-like growth factor-1 and transforming growth factor-β1 signaling pathways ( 4 , 38 – 40 ). Klotho may protect cells from oxidative stress-induced death ( 38 ).…”

Section: Discussionmentioning

confidence: 99%

“…Klotho has been shown to regulate oxidative stress, fibrosis, and inflammation through suppression of insulin/insulin-like growth factor-1 and transforming growth factor-β1 signaling pathways ( 4 , 38 – 40 ). Klotho may protect cells from oxidative stress-induced death ( 38 ). Klotho is a pleiotropic protein that has a number of beneficial effects on the endothelium.…”

Section: Discussionmentioning

confidence: 99%

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Renal Function Mediates the Association Between Klotho and Congestive Heart Failure Among Middle-Aged and Older Individuals

Zhu

Yin

et al. 2022

Front. Cardiovasc. Med.

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ObjectiveUsing a newly released National Health and Nutrition Examination Survey (NHANES) data of serum Klotho, this study aimed to explore the relationship between Klotho and specific cardiovascular diseases (CVD), as well as the mediation effect of renal function, among middle-aged and older individuals within the general population.MethodsThis nationally representative cross-sectional study analyzed data from the 2007–2016 NHANES. A total of 13,765 participants, who aged 40 years or older, from the general population were examined. Klotho were divided into four groups based on median and interquartile range. The associations among Klotho (exposure), congestive heart failure (CHF; outcome), and renal function markers [estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), uric acid (UA), and urine albumin-to-creatinine ratio (UACR); mediators] were investigated using mediation analysis.ResultsIn comparison to the lowest quartile, Klotho in the highest quartile was independently associated with the prevalence of CHF (OR 0.59; 95% CI 0.46–0.77, p for trend = 0.001), but not with other individual CVDs. Klotho had a significant direct effect on the prevalence of CHF (all p < 0.001), while eGFR, BUN, UA, and UACR partly mediated the indirect effect of Klotho on the prevalence of CHF (all p < 0.05), explaining 19.51, 6.98, 13.93, and 0.71% of the association between Klotho and CHF, respectively. Additionally, restricted cubic spline regression demonstrated a linear association and negative correlation between Klotho level and CHF.ConclusionThese findings suggest that Klotho is closely linked to CHF and renal function may be a key mediator of this association.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Renal Function Mediates the Association Between Klotho and Congestive Heart Failure Among Middle-Aged and Older Individuals

Zhu

Yin

et al. 2022

Front. Cardiovasc. Med.

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“…α-Klotho is an anti-ageing molecule, which is expressed in various tissues, including the kidney, lung, choroid plexus, and skeletal muscle 4 , 5 . The decrease in Klotho levels contributes to the occurrence and development of many diseases 6 - 8 . Serum cotinine is a sensitive and specific marker of smoking, which has proven useful in estimating the risks associated with smoking status 9 .…”

Section: Introductionmentioning

confidence: 99%

Association between serum cotinine and α-Klotho levels among adults: Findings from the National Health and Nutrition Examination Survey 2007–2016

Yao¹,

Long²,

Du³

et al. 2022

Tob. Induc. Dis.

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INTRODUCTION Serum cotinine is a sensitive and specific marker of tobacco smoke exposure. α-Klotho is an anti-ageing molecule, which plays an important role in several diseases. We aimed to examine the association between smoke exposure indicated by the serum cotinine and α-Klotho levels, as previous reports regarding the level of α-Klotho in smokers have been inconsistent. METHODS This secondary dataset analysis included 9833 participants (aged 40–79 years; 47.0% females and 53.0% males) from the US National Health and Nutrition Examination Survey 2007–2016. Independent variables were serum cotinine level, age, sex, race, body mass index (BMI), and alcohol consumption. The outcome variable was serum α-Klotho level. Multiple linear regression analysis was used to examine the association between serum cotinine and α-Klotho levels. RESULTS The serum cotinine level was negatively associated with the α-Klotho level ( β = -0.107, 95% CI: -0.155 to -0.059, p<0.0001) after adjusting for age, BMI, sex, race, and alcohol consumption. The α-Klotho level in participants with cotinine ≥3 ng/mL decreased by 44.514 pg/mL (p<0.0001) compared to that in participants with cotinine <3 ng/mL. There is a non-linear relationship between serum cotinine and α-Klotho levels. The piecewise linear models indicated a significant threshold effect between serum cotinine and α-Klotho levels. On the left of the inflection point (cotinine <130 ng/mL), the serum cotinine level increased with decreased α-Klotho level ( β = -0.519, 95% CI: -0.682 to -0.356). On the right of the inflection point (cotinine ≥130 ng/mL), the serum cotinine level increased with increased α-Klotho level ( β =0.085, 95% CI: 0.000 to 0.170). CONCLUSIONS Based on our study results, serum cotinine level was associated with the serum α-Klotho level.

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“…and its cyclic derivatives from the racetam family (phenotropil, piracetam, pramiracetam, aniracetam, phazoracetam, etc.) [2,3].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of the Psychotropic Activity of Framework Derivatives of Alpha-Pyrrolidone

et al. 2021

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Derivatives of alpha-pyrrolidone and some derivatives of adamantane possess a wide spectrum of psychotropic activity. The synthesis of adamantane and homoadamantane derivatives of alpha-pyrrolidone and the assessment of their psychotropic activity were performed. A number of framework compounds containing a pyrrolidin-2-one fragment either in the side chain or as part of the framework system were synthesized. N-(Adamantan-1-yl)pyrrolidin-2-one (TIM-2) was obtained by the reaction of 1-bromadamantane with pyrrolidin-2-one. Homoadamantane-fused pyrrolidin-2-one (TIM-1) was obtained from β-dicarbonyl derivatives of homoadamantane. Synthesis of the starting 2-(5-oxohomoadamantyl)acetic acid was carried out by cleavage of the corresponding keto diester or cyanoketo ester of homoadamantane under the conditions of the Holler-Bauer reaction with sonication. Then, the resulting γ-keto acid was introduced into the Leuckart-Wallach reaction to obtain cis- decahydro-4,8:6,10-dimethanocyclononane[b]pyrrol-2(1H)-one (TIM-1). The psychotropic activity of the obtained compounds was evaluated in standard behavioral tests in experimental animals. Compound TIM-2 exhibited pronounced anxiolytic, antidepressant, and nootropic activity. Compound binding assays were performed by molecular docking of the synthesized compounds to the GABA-B receptor, which also showed high binding energies for TIM-2.

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Klotho Protein and Cardio-Vascular System

Cited by 23 publications

References 106 publications

Renal Function Mediates the Association Between Klotho and Congestive Heart Failure Among Middle-Aged and Older Individuals

Renal Function Mediates the Association Between Klotho and Congestive Heart Failure Among Middle-Aged and Older Individuals

Association between serum cotinine and α-Klotho levels among adults: Findings from the National Health and Nutrition Examination Survey 2007–2016

Synthesis and Evaluation of the Psychotropic Activity of Framework Derivatives of Alpha-Pyrrolidone

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