ArticleCardiovascular diabetology2023
Genetic deletion of MMP12 ameliorates cardiometabolic disease by improving insulin sensitivity, systemic inflammation, and atherosclerotic features in mice.
Article in Cardiovascular diabetology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 24 citations in OpenAlex.
- Nanoparticle-Enabled Plasma Proteomics of Experimental Atherosclerosis in Mice.JACC. Basic to translational science · 2026Article
- Proteomic Signatures of High-Risk Coronary Plaque Features and Incident Events.JACC. Basic to translational science · 2026Article
- Causal effects of mental disorders on stroke subtypes: A proteome-wide Mendelian randomization and mediation analysis.Medicine · 2026Article
- Proteogenomic Analysis of Coronary Artery Calcification in Human Populations.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Proteomic aging clocks in epidemiological studies: advances, applications and prospects.Nature aging · 2026Review
- Matrix metalloproteinases and risk of cardiovascular mortality and morbidity in the United Kingdom: A prospective cohort study with machine learning analysis.Preventive medicine reports · 2026Article
- A novel plasma proteomic signature predicts long-term incident heart failure risk among persons living with HIV.medRxiv : the preprint server for health sciences · 2026Article
- Dissecting Genetic and Environmental Determinants of Plasma Molecular Signatures and Their Link to Type 2 Diabetes Risk.medRxiv : the preprint server for health sciences · 2025Article
- Resident Macrophage-Orchestrated Immune and Fibroblast Interactions in Immune Checkpoint Inhibitor-Associated Nephrotoxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Correlation between dyslipidaemia and gastric cancer: pathogenesis to prevention and treatment strategies.Lipids in health and disease · 2025Review
- Matrix Metalloproteinases: Pathophysiologic Implications and Potential Therapeutic Targets in Cardiovascular Disease.Biomolecules · 2025Review
- MMP12 deficiency attenuates menthol e-cigarette plus house dust-mite effects on pulmonary iron homeostasis and oxidative stress.Respiratory research · 2025Article
- Matrix metalloproteinase-driven epithelial-mesenchymal transition: implications in health and disease.Journal of translational medicine · 2025Review
- Impact of differentially expressed genes and proteins in donor arterial plaque on renal function recovery following allogeneic kidney transplantation.Translational andrology and urology · 2025Article
- Transcriptional Profiling of Abomasal Mucosa from Young Calves Experimentally Infected withInternational journal of molecular sciences · 2025Article
- Diabetes and calcific aortic valve disease: implications of glucose-lowering medication as potential therapy.Frontiers in pharmacology · 2025Review
- Limited Alleviation of Lysosomal Acid Lipase Deficiency by Deletion of Matrix Metalloproteinase 12.International journal of molecular sciences · 2024Article
- Identification of regulatory networks and crosstalk factors in brown adipose tissue and liver of a cold-exposed cardiometabolic mouse model.Cardiovascular diabetology · 2024Article
- Association of GWAS-Reported Variant of Matrix Metalloproteinase 12 Gene with Susceptibility to Ischemic Stroke in Southern Chinese Population.Journal of inflammation research · 2024Article
- MMP-12 and Periodontitis: Unraveling the Molecular Pathways of Periodontal Tissue Destruction.Journal of inflammation research · 2024Review
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Authors and funding
25 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundMatrix metalloproteinase 12 (MMP12) is a macrophage-secreted protein that is massively upregulated as a pro-inflammatory factor in metabolic and vascular tissues of mice and humans suffering from cardiometabolic diseases (CMDs). However, the molecular mechanisms explaining the contributions of MMP12 to CMDs are still unclear.
methodsWe investigated the impact of MMP12 deficiency on CMDs in a mouse model that mimics human disease by simultaneously developing adipose tissue inflammation, insulin resistance, and atherosclerosis. To this end, we generated and characterized low-density lipoprotein receptor (Ldlr)/Mmp12-double knockout (DKO) mice fed a high-fat sucrose- and cholesterol-enriched diet for 16-20 weeks.
resultsDKO mice showed lower cholesterol and plasma glucose concentrations and improved insulin sensitivity compared with LdlrKO mice. Untargeted proteomic analyses of epididymal white adipose tissue revealed that inflammation- and fibrosis-related pathways were downregulated in DKO mice. In addition, genetic deletion of MMP12 led to alterations in immune cell composition and a reduction in plasma monocyte chemoattractant protein-1 in peripheral blood which indicated decreased low-grade systemic inflammation. Aortic en face analyses and staining of aortic valve sections demonstrated reduced atherosclerotic plaque size and collagen content, which was paralleled by an improved relaxation pattern and endothelial function of the aortic rings and more elastic aortic sections in DKO compared to LdlrKO mice. Shotgun proteomics revealed upregulation of anti-inflammatory and atheroprotective markers in the aortas of DKO mice, further supporting our data. In humans, MMP12 serum concentrations were only weakly associated with clinical and laboratory indicators of CMDs.
conclusionWe conclude that the genetic deletion of MMP12 ameliorates obesity-induced low-grade inflammation, white adipose tissue dysfunction, biomechanical properties of the aorta, and the development of atherosclerosis. Therefore, therapeutic strategies targeting MMP12 may represent a promising approach to combat CMDs.
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