ArticleThe Journal of clinical investigation2015
Perhexiline activates KLF14 and reduces atherosclerosis by modulating ApoA-I production.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 113 citations in OpenAlex.
- The KLF14 Variant is Associated with Type 2 Diabetes and HbABiochemical genetics · 2021Trial
- Decoding the Kruppel-like Transcription Factors in Atherosclerosis: Insight from Molecular and Translational Perspectives.International journal of molecular sciences · 2025Review
- Genetic variations and functions of KLF14 in gene expression and metabolic disease development.Journal of applied genetics · 2025Review
- Adipocyte-specific Krüppel-like factor 14 overexpression confers sex-biased protection from weight gain on a high-fat diet.Physiological reports · 2025Article
- KLF14 and SREBF-1 Binding Site Associations with Orphan Receptor Promoters in Metabolic Syndrome.International journal of molecular sciences · 2025Article
- Chromatin Remodeling in Patient-Derived Colorectal Cancer Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Epigenetic modifications in obesity-associated diseases.MedComm · 2024Review
- Molecular mechanisms, targets and clinical potential of berberine in regulating metabolism: a review focussing on databases and molecular docking studies.Frontiers in pharmacology · 2024Review
- The role of transcription factors in the pathogenesis and therapeutic targeting of vascular diseases.Frontiers in cardiovascular medicine · 2024Review
- Pan-primate studies of age and sex.GeroScience · 2023Article
- Downregulation of Krüppel-like factor 14 accelerated cellular senescence and aging.Aging cell · 2023Article
- Specificity Proteins (SP) and Krüppel-like Factors (KLF) in Liver Physiology and Pathology.International journal of molecular sciences · 2023Review
- Biochemical Activation and Regulatory Functions of Trans-Regulatory KLF14 and Its Association with Genetic Polymorphisms.Metabolites · 2023Review
- KLF14 regulates the growth of hepatocellular carcinoma cells via its modulation of iron homeostasis through the repression of iron-responsive element-binding protein 2.Journal of experimental & clinical cancer research : CR · 2023Article
- Genetic Determinants of Cardiovascular Disease: The Endothelial Nitric Oxide Synthase 3 (eNOS3), Krüppel-Like Factor-14 (KLF-14), Methylenetetrahydrofolate Reductase (MTHFR), MiRNAs27a and Their Association with the Predisposition and Susceptibility to Coronary Artery Disease.Life (Basel, Switzerland) · 2022Article
- Differential Genetic and Epigenetic Effects of theInternational journal of molecular sciences · 2022Article
- Adipocyte-Specific Modulation of KLF14 Expression in Mice Leads to Sex-Dependent Impacts on Adiposity and Lipid Metabolism.Diabetes · 2022Article
- Krüppel-like factor 14 deletion in myeloid cells accelerates atherosclerotic lesion development.Cardiovascular research · 2022Article
- HDL and ASCVD.Advances in experimental medicine and biology · 2022Article
- Proteome-scale profiling reveals MAFF and MAFG as two novel key transcription factors involved in palmitic acid-induced umbilical vein endothelial cell apoptosis.BMC cardiovascular disorders · 2021Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Recent genome-wide association studies have revealed that variations near the gene locus encoding the transcription factor Krüppel-like factor 14 (KLF14) are strongly associated with HDL cholesterol (HDL-C) levels, metabolic syndrome, and coronary heart disease. However, the precise mechanisms by which KLF14 regulates lipid metabolism and affects atherosclerosis remain largely unexplored. Here, we report that KLF14 is dysregulated in the liver of 2 dyslipidemia mouse models. We evaluated the effects of both KLF14 overexpression and genetic inactivation and determined that KLF14 regulates plasma HDL-C levels and cholesterol efflux capacity by modulating hepatic ApoA-I production. Hepatic-specific Klf14 deletion in mice resulted in decreased circulating HDL-C levels. In an attempt to pharmacologically target KLF14 as an experimental therapeutic approach, we identified perhexiline, an approved therapeutic small molecule presently in clinical use to treat angina and heart failure, as a KLF14 activator. Indeed, in WT mice, treatment with perhexiline increased HDL-C levels and cholesterol efflux capacity via KLF14-mediated upregulation of ApoA-I expression. Moreover, perhexiline administration reduced atherosclerotic lesion development in apolipoprotein E-deficient mice. Together, these results provide comprehensive insight into the KLF14-dependent regulation of HDL-C and subsequent atherosclerosis and indicate that interventions that target the KLF14 pathway should be further explored for the treatment of atherosclerosis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.