Participation of Krüppel-like Factors in Atherogenesis

Kotlyarov, Stanislav; Kotlyarova, Anna

doi:10.3390/metabo13030448

Cited by 7 publications

(5 citation statements)

References 177 publications

(258 reference statements)

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“…Another important function of KLF4 is its involvement in cross-linking with cellular metabolism [ 53 ]. Glycolysis is known to be the major energy source for endothelial cells, producing up to 85% of ATP [ 54 , 55 , 56 , 57 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Atherogenic Factors on Endothelial Cells: Bioinformatics Analysis of Differentially Expressed Genes and Signaling Pathways

Kotlyarov

2023

Biomedicines

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(1) Background: Atherosclerosis is a serious medical condition associated with high morbidity and mortality rates. It develops over many years as a complex chain of events in the vascular wall involving various cells and is influenced by many factors of clinical interest. (2) Methods: In this study, we performed a bioinformatic analysis of Gene Expression Omnibus (GEO) datasets to investigate the gene ontology of differentially expressed genes (DEGs) in endothelial cells exposed to atherogenic factors such as tobacco smoking, oscillatory shear, and oxidized low-density lipoproteins (oxLDL). DEGs were identified using the limma R package, and gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein–protein interaction (PPI) network analysis were performed. (3) Results: We studied biological processes and signaling pathways involving DEGs in endothelial cells under the influence of atherogenic factors. GO enrichment analysis demonstrated that the DEGs were mainly involved in cytokine-mediated signaling pathway, innate immune response, lipid biosynthetic process, 5-lipoxygenase activity, and nitric-oxide synthase activity. KEGG pathway enrichment analysis showed that common pathways included tumor necrosis factor signaling pathway, NF-κB signaling pathway, NOD-like receptor signaling pathway, lipid and atherosclerosis, lipoprotein particle binding, and apoptosis. (4) Conclusions: Atherogenic factors such as smoking, impaired flow, and oxLDL contribute to impaired innate immune response, metabolism, and apoptosis in endothelial cells, potentially leading to the development of atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Effects of Atherogenic Factors on Endothelial Cells: Bioinformatics Analysis of Differentially Expressed Genes and Signaling Pathways

Kotlyarov

2023

Biomedicines

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“…As our study centered only on the CACCC-box motif from 150 bp upstream to 300 bp downstream of the TATA-box, hence other relevant KLF binding motifs such as GC-rich regions GC-and GT-were not explored. Therefore, several previously identified genes known to be regulated by KLFs and several processes were not enriched during this study, such as vascular wall homeostasis and atherosclerosis [58,59].…”

Section: Limitationsmentioning

confidence: 91%

Is the Cis-Element CACCC-Box a Master Regulatory Element during Cardiovascular Disease? A Bioinformatics Approach from the Perspective of the Krüppel-like Family of Transcription Factors

García-Loredo,

Santoyo-Suarez,

Rodríguez-Nuñez

et al. 2024

Life

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The CACCC-box motif emerges as a pivotal cis-regulatory element implicated in diverse developmental processes and diseases, particularly cardiovascular diseases (CVDs). This study centers on the intricate interplay between the CACCC-box and its binding proteins such as: the Krüppel-Like Family (KLF) of transcription factors as primary effectors in the context of CVDs. Our analysis was through a bioinformatics approach, which revealed significant transcriptional activity among KLF subgroup 2, exhibiting the highest number of interactions focusing on the established roles: pluripotency, cancer, and cardiovascular development and diseases. Our analysis reveals KLF’s interactions with GATA4, MEF2C, NKX2.5 and other ~90 potential genes that participate in the regulation of the hypertrophic environment (or CVDs’ Environment). Also, the GO analysis showed that genes containing the motif CACCC were enriched for multiple CVDs; in combination with STRING analysis, these results pointed to a link between KLFs and these diseases. The analysis further identifies other potential CACCC-box binding factors, such as SP family members, WT1, VEZF1, and -SALL4, which are implicated in cardiac contraction, remodeling, and inflammation processes.

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“…Although KLFs are found in multiple organ systems, including the cardiovascular, respiratory, gastrointestinal, urinary, neurological, and hematopoietic systems ( 15 ), their tissue expression varies ( Figure 1 ). In other words, some family members are universally expressed, while others are specifically expressed ( 16 – 18 ). Studies have shown that KLFs possess three highly conserved C2H2 zinc-finger domains in their carboxy-terminal region.…”

Section: Krüppel-like Factorsmentioning

confidence: 99%

Krüpple-like factors in cardiomyopathy: emerging player and therapeutic opportunities

Gui,

Liu,

Jin

et al. 2024

Front. Cardiovasc. Med.

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Cardiomyopathy, a heterogeneous pathological condition characterized by changes in cardiac structure or function, represents a significant risk factor for the prevalence and mortality of cardiovascular disease (CVD). Research conducted over the years has led to the modification of definition and classification of cardiomyopathy. Herein, we reviewed seven of the most common types of cardiomyopathies, including Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), diabetic cardiomyopathy, Dilated Cardiomyopathy (DCM), desmin-associated cardiomyopathy, Hypertrophic Cardiomyopathy (HCM), Ischemic Cardiomyopathy (ICM), and obesity cardiomyopathy, focusing on their definitions, epidemiology, and influencing factors. Cardiomyopathies manifest in various ways ranging from microscopic alterations in cardiomyocytes, to tissue hypoperfusion, cardiac failure, and arrhythmias caused by electrical conduction abnormalities. As pleiotropic Transcription Factors (TFs), the Krüppel-Like Factors (KLFs), a family of zinc finger proteins, are involved in regulating the setting and development of cardiomyopathies, and play critical roles in associated biological processes, including Oxidative Stress (OS), inflammatory reactions, myocardial hypertrophy and fibrosis, and cellular autophagy and apoptosis, particularly in diabetic cardiomyopathy. However, research into KLFs in cardiomyopathy is still in its early stages, and the pathophysiologic mechanisms of some KLF members in various types of cardiomyopathies remain unclear. This article reviews the roles and recent research advances in KLFs, specifically those targeting and regulating several cardiomyopathy-associated processes.

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Participation of Krüppel-like Factors in Atherogenesis

Cited by 7 publications

References 177 publications

Effects of Atherogenic Factors on Endothelial Cells: Bioinformatics Analysis of Differentially Expressed Genes and Signaling Pathways

Effects of Atherogenic Factors on Endothelial Cells: Bioinformatics Analysis of Differentially Expressed Genes and Signaling Pathways

Is the Cis-Element CACCC-Box a Master Regulatory Element during Cardiovascular Disease? A Bioinformatics Approach from the Perspective of the Krüppel-like Family of Transcription Factors

Krüpple-like factors in cardiomyopathy: emerging player and therapeutic opportunities

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