ArticleCell reports2015
Impaired LRP6-TCF7L2 Activity Enhances Smooth Muscle Cell Plasticity and Causes Coronary Artery Disease.
Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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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.
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Who cites it
46 citing papers in PubMed, 72 citations in OpenAlex.
- TCF7L2 promotes abdominal aortic aneurysm through smooth muscle cell-mediated extracellular matrix remodeling.JCI insight · 2026Article
- Evaluation of the cellular impact of missense variants in low-density lipoprotein receptor-related protein 6 (LRP6) associated with cardiovascular diseases in HeLa and HEK293T cell lines.Frontiers in cell and developmental biology · 2026Article
- What Causes Premature Coronary Artery Disease?Current atherosclerosis reports · 2024Review
- Identifying Genetic Signatures Associated with Oncogene-Induced Replication Stress in Osteosarcoma and Screening for Potential Targeted Drugs.Biochemical genetics · 2024Article
- Single-Cell Analyses Offer Insights into the Different Remodeling Programs of Arteries and Veins.Cells · 2024Article
- Wnt16 Promotes Vascular Smooth Muscle Contractile Phenotype and Function via Taz (Wwtr1) Activation in Male LDLR-/- Mice.Endocrinology · 2023Article
- Rottlerin suppresses lipid accumulation by inhibiting de novo lipogenesis and adipogenesis via LRP6/mTOR/SREBP1C in 3T3-L1 adipocytes.Food science and biotechnology · 2023Article
- TCF7L1 Accelerates Smooth Muscle Cell Phenotypic Switching and Aggravates Abdominal Aortic Aneurysms.JACC. Basic to translational science · 2023Article
- Molecular Mechanisms of Vascular Health: Insights From Vascular Aging and Calcification.Arteriosclerosis, thrombosis, and vascular biology · 2023Review
- Non-canonical WNT signalling in cardiovascular disease: mechanisms and therapeutic implications.Nature reviews. Cardiology · 2022Review
- Identification of Key Genes in Atherosclerosis by Combined DNA Methylation and miRNA Expression Analyses.Anatolian journal of cardiology · 2022Article
- The Contribution of Wnt Signaling to Vascular Complications in Type 2 Diabetes Mellitus.International journal of molecular sciences · 2022Review
- Review
- Levels of miR-130b-5p in peripheral blood are associated with severity of coronary artery disease.Molecular biology reports · 2021Article
- Regulatory variants in TCF7L2 are associated with thoracic aortic aneurysm.American journal of human genetics · 2021Article
- The complex role of Wnt ligands in type 2 diabetes mellitus and related complications.Journal of cellular and molecular medicine · 2021Review
- Association of Combined TCF7L2 and KCNQ1 Gene Polymorphisms with Diabetic Micro- and Macrovascular Complications in Type 2 Diabetes Mellitus.Diabetes & metabolism journal · 2021Article
- LRP6 downregulation promotes cardiomyocyte proliferation and heart regeneration.Cell research · 2021Article
- Transcriptome Analysis Reveals the Profile of Long Non-coding RNAs During Chicken Muscle Development.Frontiers in physiology · 2021Article
- Wnt Signaling Cascades and Their Role in Coronary Artery Health and Disease.Journal of cellular signaling · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in Wnt-signaling coreceptor LRP6 have been linked to coronary artery disease (CAD) by unknown mechanisms. Here, we show that reduced LRP6 activity in LRP6(R611C) mice promotes loss of vascular smooth muscle cell (VSMC) differentiation, leading to aortic medial hyperplasia. Carotid injury augmented these effects and led to partial to total vascular obstruction. LRP6(R611C) mice on high-fat diet displayed dramatic obstructive CAD and exhibited an accelerated atherosclerotic burden on LDLR knockout background. Mechanistically, impaired LRP6 activity leads to enhanced non-canonical Wnt signaling, culminating in diminished TCF7L2 and increased Sp1-dependent activation of PDGF signaling. Wnt3a administration to LRP6(R611C) mice improved LRP6 activity, led to TCF7L2-dependent VSMC differentiation, and rescued post-carotid-injury neointima formation. These findings demonstrate the critical role of intact Wnt signaling in the vessel wall, establish a causal link between impaired LRP6/TCF7L2 activities and arterial disease, and identify Wnt signaling as a therapeutic target against CAD.
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Registered trials
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 OpenQuestion graph.