ArticleNature cardiovascular research2024
Endothelial γ-protocadherins inhibit KLF2 and KLF4 to promote atherosclerosis.
Article in Nature cardiovascular research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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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
22 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Mechanopriming by vascular stiffness and phenotypic reprogramming by disturbed flow: mechanobiology and clinical translation in atherosclerosis.Frontiers in cardiovascular medicine · 2026Pooled it
- KLF transcription factors in metabolic kidney disease: from podocyte protection to tubulointerstitial fibrosis.International urology and nephrology · 2026Review
- Polycomb Repressive Complex 2 drives flow-sensitive endothelial states underlying vascular inflammation and disease.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Local pressure as a dominant hemodynamic driver of wall enhancement in anterior communicating artery aneurysms: a facet-level computational fluid dynamics and vessel wall imaging analysis.Quantitative imaging in medicine and surgery · 2026Article
- Integrated Epidemiological and Extracellular Vesicle Profiling Identifies miR-126-3p, miR-21-5p, miR-92a-3p and SNAIL as Candidate Biomarkers of Endothelial Dysfunction and Cardio-Metabolic Risk.International journal of molecular sciences · 2026Article
- Inflammation in atherosclerosis: Drivers, mechanisms and therapies.Acta pharmaceutica Sinica. B · 2026Review
- Tnxb Alleviates Myocardial Ischemia-Reperfusion Injury Through Facilitating Akt-Dependent Endothelial Cell Survival and Angiogenesis in Mice.Cardiovascular toxicology · 2026Article
- Exercise-Induced Shear Stress, Endothelial Glycocalyx Remodeling, and Atherosclerotic Plaque Stability: A Mechanistic Review.Journal of cardiovascular development and disease · 2026Review
- Non-coding RNAs in lipid metabolism and their roles in atherosclerosis.Nature reviews. Cardiology · 2026Review
- Deletion of endothelial KLF4 as a model for preeclampsia.bioRxiv : the preprint server for biology · 2026Article
- Endothelial senescence of the vertebral artery in the context of cervical degeneration: biomechanically driven remodeling of the hemodynamic environment.Frontiers in cell and developmental biology · 2026Review
- Research progress on targeted regulatory proteins in the prevention and treatment of atherosclerosis.Frontiers in immunology · 2026Review
- Spatial architecture of atherosclerotic plaques: coordinating immune responses through mechanotransduction and vesicular trafficking.Frontiers in cell and developmental biology · 2026Review
- Aortic dissection as a disease of vascular wall homeostasis: integrating vasa vasorum-inflammation-metabolism axis for mechanistic insight and clinical translation.Frontiers in immunology · 2026Review
- Endothelial Klf9 fine-tunes Akt signaling to act as a transcriptional brake restraining retinal angiogenesis.International journal of biological sciences · 2026Article
- Sentrin-specific protease 3 (SENP3)-mediated Krüppel-like factor 4 (KLF4) deSUMOylation regulates vascular smooth muscle cell phenotypic switching in atherosclerosis.Molecular biomedicine · 2025Article
- Roles of Autophagy and Oxidative Stress in Cardiovascular Disease.Antioxidants (Basel, Switzerland) · 2025Review
- Fluid Shear Stress-Regulated Vascular Remodeling: Past, Present, and Future.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Glycometabolic Regulation of Angiogenesis: Mechanisms and Therapeutic Strategies.International journal of molecular sciences · 2025Review
- A New Targeted Transgenic Mouse Line for the Study of Protocadherin γC4.Genesis (New York, N.Y. : 2000) · 2025Article
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Abstract
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Laminar shear stress from blood flow, sensed by vascular endothelial cells, protects from ASCVD by upregulating the transcription factors KLF2 and KLF4, which induces an anti-inflammatory program that promotes vascular resilience. Here we identify clustered γ-protocadherins as therapeutically targetable, potent KLF2 and KLF4 suppressors whose upregulation contributes to ASCVD. Mechanistic studies show that γ-protocadherin cleavage results in translocation of the conserved intracellular domain to the nucleus where it physically associates with and suppresses signaling by the Notch intracellular domain. γ-Protocadherins are elevated in human ASCVD endothelium; their genetic deletion or antibody blockade protects from ASCVD in mice without detectably compromising host defense against bacterial or viral infection. These results elucidate a fundamental mechanism of vascular inflammation and reveal a method to target the endothelium rather than the immune system as a protective strategy in ASCVD.
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