ArticleProceedings of the National Academy of Sciences of the United States of America2020
Clonally expanding smooth muscle cells promote atherosclerosis by escaping efferocytosis and activating the complement cascade.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 125 citations in OpenAlex.
- Clonal hematopoiesis of indeterminate potential (CHIP), vascular somatic mutation, and cardiovascular disease: A narrative review.Vascular medicine (London, England) · 2026Review
- Single-cell transcriptomics reveals cell-type-specific circadian rhythms and their disruption by acute misalignment in mouse aorta.bioRxiv : the preprint server for biology · 2026Article
- Cell-Surface Signatures and Targets of Modulated Vascular Smooth Muscle Cells in Atherosclerosis: From State Identification to Precision Intervention.Journal of cardiovascular development and disease · 2026Review
- Loss of the Coronary Artery Disease Risk GeneCirculation · 2026Article
- Nanomaterials-Based Immunotherapy for Atherosclerosis.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Single-cell transcriptomics uncovers endothelial progenitor-like remodelling driving human coronary atherosclerosis progression.Nature cell biology · 2026Article
- Vascular Smooth Muscle Cell Plasticity in Atherosclerosis: Mechanisms, Recent Advances, and Therapeutic Implications.Reviews in cardiovascular medicine · 2026Review
- Conditional knockout of membrane-type I matrix metalloproteinase in smooth muscle cells of adult mice alleviates atherosclerosis without affecting basic cardiovascular function.Clinical and translational medicine · 2026Article
- HDL Regulates TGFβ-Receptor Lipid Raft Partitioning, Restoring Contractile Features of Cholesterol-Loaded Vascular Smooth Muscle Cells.JACC. Basic to translational science · 2026Article
- A Comprehensive Review of Epigenetic Regulation of Vascular Smooth Muscle Cells During Development and Disease.Biomolecules · 2026Review
- Efferocytosis: unifying pathogenic hub in metabolic disorders-mechanistic landscapes, targeted therapies and translational bottlenecks.Frontiers in immunology · 2026Review
- Immune checkpoint inhibitor-induced cardiotoxicity: from immune mechanisms to clinical surveillance and targeted therapies.Frontiers in cardiovascular medicine · 2026Review
- The Pathophysiology of Coronary Artery Disease.The International journal of angiology : official publication of the International College of Angiology, Inc · 2025Review
- Smooth muscle cells in atherosclerosis: essential but overlooked translational perspectives.European heart journal · 2025Review
- Innate immune cells in vascular lesions: mechanism and significance of diversified immune regulation.Annals of medicine · 2025Review
- Role of Matricellular Proteins in Endothelial Cell Inflammation and Atherosclerosis.Antioxidants (Basel, Switzerland) · 2025Review
- Complement C3 in panvascular disease: a central integrator of immune signaling and vascular remodeling.Clinical science (London, England : 1979) · 2025Review
- Functional Roles of the Complement Immune System in Cardiac Inflammation and Hypertrophy.International journal of molecular sciences · 2025Review
- Cancer-Related Immune Therapies: Bidirectional Implications From Cardiotoxicity to Emerging Cardiovascular Therapeutics: JACC CardioOncology State-of-the-Art Review.JACC. CardioOncology · 2025Review
- The immune system in cardiovascular diseases: from basic mechanisms to therapeutic implications.Signal transduction and targeted therapy · 2025Review
33 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 9 institutions in 5 countries.
Funding
Abstract
Atherosclerosis is the process underlying heart attack and stroke. Despite decades of research, its pathogenesis remains unclear. Dogma suggests that atherosclerotic plaques expand primarily via the accumulation of cholesterol and inflammatory cells. However, recent evidence suggests that a substantial portion of the plaque may arise from a subset of "dedifferentiated" vascular smooth muscle cells (SMCs) which proliferate in a clonal fashion. Herein we use multicolor lineage-tracing models to confirm that the mature SMC can give rise to a hyperproliferative cell which appears to promote inflammation via elaboration of complement-dependent anaphylatoxins. Despite being extensively opsonized with prophagocytic complement fragments, we find that this cell also escapes immune surveillance by neighboring macrophages, thereby exacerbating its relative survival advantage. Mechanistic studies indicate this phenomenon results from a generalized opsonin-sensing defect acquired by macrophages during polarization. This defect coincides with the noncanonical up-regulation of so-called don't eat me molecules on inflamed phagocytes, which reduces their capacity for programmed cell removal (PrCR). Knockdown or knockout of the key antiphagocytic molecule CD47 restores the ability of macrophages to sense and clear opsonized targets in vitro, allowing for potent and targeted suppression of clonal SMC expansion in the plaque in vivo. Because integrated clinical and genomic analyses indicate that similar pathways are active in humans with cardiovascular disease, these studies suggest that the clonally expanding SMC may represent a translational target for treating atherosclerosis.
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