Left ventricular hypertrophy in experimental chronic kidney disease is associated with reduced expression of cardiac Kruppel-like factor 15

Patel, Sheila K.; Velkoska, Elena; Gayed, D.; Ramchand, Jay; Lesmana, Jessica; Burrell, Louise M.

doi:10.1186/s12882-018-0955-9

Cited by 8 publications

(3 citation statements)

References 41 publications

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“…Our results suggest that sex-specific changes in CKDrelated cardiac structural remodeling are present in this mouse model. Considering that LV hypertrophy is a common morphology that can predict the risk of adverse cardiovascular events in CKD patients, and that sex differences exist in the manifestation and progression of CKD in humans, with female sex being a protective factor in CKD-associated CVD risk, we conclude that an advantage of this model is its ability to study these CKD-induced CVD sex differences 31,32 .…”

Section: Discussionmentioning

confidence: 98%

Sex-Specific Changes in Cardiac Function and Electrophysiology During Progression of Adenine-Induced Chronic Kidney Disease in Mice

Dargam,

Sanchez,

Kolengaden

et al. 2024

Preprint

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BACKGROUNDChronic kidney disease (CKD) and cardiovascular disease (CVD) often co-exist and interact; however, notable sex-dependent differences are observed in how these conditions manifest and progress in parallel, despite men and women sharing similar risk factors. Identifying sex-specific diagnostic markers of cardiac structure and function throughout CKD progression could elucidate why the development and progression of these diseases differ by sex.METHODS AND RESULTSAdult, C57BL/6J male and female mice were subjected to a high-adenine (0.2%) diet throughout 12-weeks to induce CKD. Control mice were fed a normal chow diet. Every three weeks, electrocardiogram (ECG) and echocardiogram-based markers of cardiac physiology were evaluated. Adenine-induced CKD showed markers of left ventricular (LV) hypertrophy in male mice only. CKD males had markers indicative of LV systolic and diastolic dysfunction throughout regimen duration, worsening as disease progressed. Adenine males had a prolonged QTc and STc intervals when compared to Adenine females and Control males. Sex-dependent differences in the duration of the Speak-J marker, measured via ECG, was identified, with Adenine males showing increases in duration earlier than Adenine females compared to their Control counterparts.CONCLUSIONSIn this study, we identified sex-dependent differences in cardiac structure, function, and electrophysiology in a mouse model of CKD-induced CVD throughout disease progression. We found that male mice are more prone to developing LV hypertrophy, systolic dysfunction, and diastolic dysfunction, with significant increases in ECG markers indicative of ventricular dysfunction observed in adenine-treated males at late stages of the disease. Additionally, we identified a new ECG parameter, Speak-J duration, that highlights sex-specific cardiac electrophysiological changes, demonstrating the model’s utility in studying sex-dependent cardiac differences.

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Section: Discussionmentioning

confidence: 98%

Sex-Specific Changes in Cardiac Function and Electrophysiology During Progression of Adenine-Induced Chronic Kidney Disease in Mice

Dargam,

Sanchez,

Kolengaden

et al. 2024

Preprint

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“…It has been shown that KLF15 is an important negative regulator of cardiac hypertrophy, and loss or repression of KLF15 leads to left ventricle hypertrophy, due to lack of inhibition of pro-hypertrophic transcription factors and stimulation of trophic and fibrotic signaling pathways [ 50 ]. Importantly, single nucleotide polymorphisms in KLF15 have been associated with cardiac hypertrophy in patients with diabetes mellitus [ 51 ], and in experimental chronic kidney disease, ventricular hypertrophy is associated with reduced expression of cardiac KLF15 [ 52 ]. In the present study, two AF patients in this family developed left ventricle hypertrophy, highlighting the need for regular echocardiographic evaluation of cardiac structure and function for the mutation carriers to make an early diagnosis of left ventricle hypertrophy, a common harbinger of heart failure and sudden cardiac death.…”

Section: Discussionmentioning

confidence: 99%

KLF15 Loss-of-Function Mutation Underlying Atrial Fibrillation as well as Ventricular Arrhythmias and Cardiomyopathy

Shi

et al. 2021

Genes

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Atrial fibrillation (AF) represents the most common type of clinical cardiac arrhythmia and substantially increases the risks of cerebral stroke, heart failure and death. Accumulating evidence has convincingly demonstrated the strong genetic basis of AF, and an increasing number of pathogenic variations in over 50 genes have been causally linked to AF. Nevertheless, AF is of pronounced genetic heterogeneity, and the genetic determinants underpinning AF in most patients remain obscure. In the current investigation, a Chinese pedigree with AF as well as ventricular arrhythmias and hypertrophic cardiomyopathy was recruited. Whole exome sequencing and bioinformatic analysis of the available family members were conducted, and a novel heterozygous variation in the KLF15 gene (encoding Krüppel-like factor 15, a transcription factor critical for cardiac electrophysiology and structural remodeling), NM_014079.4: c.685A>T; p.(Lys229*), was identified. The variation was verified by Sanger sequencing and segregated with autosomal dominant AF in the family with complete penetrance. The variation was absent from 300 unrelated healthy subjects used as controls. In functional assays using a dual-luciferase assay system, mutant KLF15 showed neither transcriptional activation of the KChIP2 promoter nor transcriptional inhibition of the CTGF promoter, alone or in the presence of TGFB1, a key player in the pathogenesis of arrhythmias and cardiomyopathies. The findings indicate KLF15 as a new causative gene responsible for AF as well as ventricular arrhythmias and hypertrophic cardiomyopathy, and they provide novel insight into the molecular mechanisms underlying cardiac arrhythmias and hypertrophic cardiomyopathy.

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“… 9 In patients with hypertension, the period of high pressure reaches 160-190mmhg and low pressure reaches 100-109 is clinically characterized by LVH and organic diseases in the heart, brain and kidney system. 10 , 11 The heart and blood vessels are the main target organs for the pathophysiological effects of hypertension. Hypertensive heart disease, characterized by symmetrical hypertrophy, asymmetric hypertrophy and extendible hypertrophy, is known as hypertensive heart disease due to cardiac hypertrophy and expansion caused by long-term high pressure load, cardiomyocyte hypertrophy and interstitial fibrosis changes.…”

Section: Discussionmentioning

confidence: 99%

Study on the correlation between Left Ventricular Hypertrophy and Coronary Artery disease in the very elderly patients with hypertension

Sun¹,

Liu

Zhang³

et al. 2021

Pak J Med Sci

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Objective: To investigate the relationship between left ventricular hypertrophy (LVH) and coronary artery disease in the very elderly (over 80 years old) patients with hypertension. Methods: One hundred twenty cases of very elderly patients with hypertension admitted to our hospital from March 2018 to December 2020 were selected and divided into two groups: the LVH group and the non-LVH group, all of whom were older aged over 80 years, including 62 patients in the LVH group and 58 patients in the non-LVH group. All patients underwent cardiac color Doppler ultrasound examination, 24-hour dynamic ECG examination, and coronary angiography or coronary CTA examination. The clinical data of the two groups were analyzed statistically. Results: There were significant differences in the number of diseased vessels, degree of coronary stenosis and vascular calcification between the two groups (P<0.05). Moreover, the results of risk factors for the degree of coronary artery disease in the two groups showed that the history of diabetes, 2hPG and LVH were independent risk factors for the three-vessel disease, while the history of LVH, FPG and alcohol intake were independent risk factors for diffuse lesions, but there was no statistical difference in the correlation between them and the degree of coronary stenosis. Conclusion: LVH is an independent risk factor for coronary artery stenosis and calcification in the very elderly patients with hypertension, but there is no statistical difference in the correlation between LVH and the degree of coronary stenosis. doi: https://doi.org/10.12669/pjms.37.5.4135 How to cite this:Sun JH, Liu XK, Zhang Q, Zhang QH. Study on the correlation between Left Ventricular Hypertrophy and Coronary Artery disease in the very elderly patients with hypertension. Pak J Med Sci. 2021;37(5):---------. doi: https://doi.org/10.12669/pjms.37.5.4135 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Left ventricular hypertrophy in experimental chronic kidney disease is associated with reduced expression of cardiac Kruppel-like factor 15

Cited by 8 publications

References 41 publications

Sex-Specific Changes in Cardiac Function and Electrophysiology During Progression of Adenine-Induced Chronic Kidney Disease in Mice

Sex-Specific Changes in Cardiac Function and Electrophysiology During Progression of Adenine-Induced Chronic Kidney Disease in Mice

KLF15 Loss-of-Function Mutation Underlying Atrial Fibrillation as well as Ventricular Arrhythmias and Cardiomyopathy

Study on the correlation between Left Ventricular Hypertrophy and Coronary Artery disease in the very elderly patients with hypertension

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