ArticleNature communications2021
Membrane type 1 matrix metalloproteinase promotes LDL receptor shedding and accelerates the development of atherosclerosis.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 56 citations in OpenAlex.
- 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
- Gender differences in the plasma profiles of proprotein convertase subtilisin/kexin-type 9 (PCSK9), soluble low-density lipoprotein receptor (sLDLR), total cholesterol, and triglycerides in patients with colorectal cancer liver metastases: diagnostic and prognostic implications.Lipids in health and disease · 2026Article
- Associations of plasma level of soluble LDL receptor with cardiovascular events and mortality in a large prospective cohort study.Lipids in health and disease · 2026Article
- Hepatic Cholesterol Regulation Through Multi-Botanical Extract Targeting of the PCSK9-LDLr-SREBP-2 Axis in HepG2 Cells.Biomedicines · 2026Article
- Ratio-Driven Lipoprotein Mapping Refines Genetic Pathways of Cardiometabolic Risk.Research square · 2026Article
- Genetic subtyping of obesity reveals biological insights into the uncoupling of adiposity from its cardiometabolic comorbidities.Nature medicine · 2025Article
- Epithelial sodium channel in dendritic cells participates in high-fat-induced inflammatory responses.Molecular biology reports · 2025Article
- IMM-H007 promotes hepatic cholesterol and triglyceride metabolism by activating AMPKActa pharmaceutica Sinica. B · 2025Article
- Pathways and Molecular Mechanisms Governing LDL Receptor Regulation.Circulation research · 2025Review
- Mmp14-dependent remodeling of the pericellular-dermal collagen interface governs fibroblast survival.The Journal of cell biology · 2024Article
- Beyond ribosomal function: RPS6 deficiency suppresses cholangiocarcinoma cell growth by disrupting alternative splicing.Acta pharmaceutica Sinica. B · 2024Article
- Hepatocyte MMP14 mediates liver and inter-organ inflammatory responses to diet-induced liver injury.PNAS nexus · 2024Article
- Functional Roles of Furin in Cardio-Cerebrovascular Diseases.ACS pharmacology & translational science · 2024Review
- Post-translational regulation of the low-density lipoprotein receptor provides new targets for cholesterol regulation.Biochemical Society transactions · 2024Article
- Redefining metalloproteases specificity through network proteolysis.Trends in molecular medicine · 2024Review
- Hepatic Surf4 Deficiency Impairs Serum Amyloid A1 Secretion and Attenuates Liver Fibrosis in Mice.Research (Washington, D.C.) · 2024Article
- Cellular and functional evaluation of LDLR missense variants reported in hypercholesterolemic patients demonstrates their hypomorphic impacts on trafficking and LDL internalization.Frontiers in cell and developmental biology · 2024Article
- Circulating biomarkers of cardiovascular disease are related to aneurysm volume in abdominal aortic aneurysm.Vascular medicine (London, England) · 2023Article
- Proteolysis of the low-density lipoprotein receptor in hepatocytes is mediated by BMP1 but not by other astacin proteases.FEBS letters · 2023Article
- Proteolytic regulation of a galectin-3/Lrp1 axis controls osteoclast-mediated bone resorption.The Journal of cell biology · 2023Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Plasma low-density lipoprotein (LDL) is primarily cleared by LDL receptor (LDLR). LDLR can be proteolytically cleaved to release its soluble ectodomain (sLDLR) into extracellular milieu. However, the proteinase responsible for LDLR cleavage is unknown. Here we report that membrane type 1-matrix metalloproteinase (MT1-MMP) co-immunoprecipitates and co-localizes with LDLR and promotes LDLR cleavage. Plasma sLDLR and cholesterol levels are reduced while hepatic LDLR is increased in mice lacking hepatic MT1-MMP. Opposite effects are observed when MT1-MMP is overexpressed. MT1-MMP overexpression significantly increases atherosclerotic lesions, while MT1-MMP knockdown significantly reduces cholesteryl ester accumulation in the aortas of apolipoprotein E (apoE) knockout mice. Furthermore, sLDLR is associated with apoB and apoE-containing lipoproteins in mouse and human plasma. Plasma levels of sLDLR are significantly increased in subjects with high plasma LDL cholesterol levels. Thus, we demonstrate that MT1-MMP promotes ectodomain shedding of hepatic LDLR, thereby regulating plasma cholesterol levels and the development of atherosclerosis.
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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.