ArticleCardiovascular research2016
Differential effects of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 on atherosclerosis and monocyte/macrophage invasion.
Article in Cardiovascular research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.
What it found
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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
33 citing papers in PubMed, 65 citations in OpenAlex.
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- Antiatherogenic and plaque stabilizing effects of saffron ethanolic extract in atherosclerotic rabbits.BMC complementary medicine and therapies · 2025Article
- The Dual Role of Oxidative Stress in Atherosclerosis and Coronary Artery Disease: Pathological Mechanisms and Diagnostic Potential.Antioxidants (Basel, Switzerland) · 2025Review
- Inflammatory crosstalk impairs phagocytic receptors and aggravates atherosclerosis in clonal hematopoiesis in mice.The Journal of clinical investigation · 2024Article
- Deep Learning and Single-Cell Sequencing Analyses Unveiling Key Molecular Features in the Progression of Carotid Atherosclerotic Plaque.Journal of cellular and molecular medicine · 2024Article
- Unveiling TIMPs: A Systematic Review of Their Role as Biomarkers in Atherosclerosis and Coronary Artery Disease.Diseases (Basel, Switzerland) · 2024Review
- Network-based prioritization and validation of regulators of vascular smooth muscle cell proliferation in disease.Nature cardiovascular research · 2024Article
- Pharmacological Inhibition of MMP-12 Exerts Protective Effects on Angiotensin II-Induced Abdominal Aortic Aneurysms in Apolipoprotein E-Deficient Mice.International journal of molecular sciences · 2024Article
- The TIMP protein family: diverse roles in pathophysiology.American journal of physiology. Cell physiology · 2024Review
- MiR-483-5p downregulation alleviates ox-LDL induced endothelial cell injury in atherosclerosis.BMC cardiovascular disorders · 2023Article
- ADAMTS-7 Modulates Atherosclerotic Plaque Formation by Degradation of TIMP-1.Circulation research · 2023Article
- Article
- Alternative polyadenylation regulation in cardiac development and cardiovascular disease.Cardiovascular research · 2023Review
- Matrix Metalloproteinases in Cardioembolic Stroke: From Background to Complications.International journal of molecular sciences · 2023Review
- The contribution of matrix metalloproteinases and their inhibitors to the development, progression, and rupture of abdominal aortic aneurysms.Frontiers in cardiovascular medicine · 2023Review
- Cationic Polyethyleneimine (PEI)-Gold Nanocomposites Modulate Macrophage Activation and Reprogram Mouse Breast Triple-Negative MET-1 Tumor Immunological Microenvironment.Pharmaceutics · 2022Article
- Review
- The Biology and Function of Tissue Inhibitor of Metalloproteinase 2 in the Lungs.Pulmonary medicine · 2022Review
- The Effects of Exercise on Plaque Volume and Composition in a Mouse Model of Early and Late Life Atherosclerosis.Frontiers in cardiovascular medicine · 2022Article
Corrections and comments
- Erratum issuedCorrigendum.2016
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
aimsMMPs contribute to atherosclerotic plaque progression and instability, but the relative potency of their endogenous tissue inhibitors of metalloproteinases (TIMPs) as protective factors has not been defined. We therefore investigated the impact of TIMP-1 and TIMP-2 knockout on atherosclerotic plaque burden and composition in apolipoprotein E-knockout (Apoe(-/-)) mice and studied the underlying effects on monocyte/macrophage behaviour. METHODS AND
resultsAnalysis of brachiocephalic artery plaques revealed comparable atherosclerotic lesion areas between TIMP-1(-/-) Apoe(-/-) or TIMP-2(-/-) Apoe(-/-) double deficient mice and relevant age-matched, strain-matched Apoe(-/-) controls after 8 weeks of high-fat feeding. However, lesions from TIMP-2(-/-) Apoe(-/-) mice had higher levels of markers associated with plaque vulnerability, including increased macrophage: vascular smooth muscle cell ratios, larger necrotic core areas, reduced collagen contents, increased macrophage proliferation, and apoptosis frequencies, compared with TIMP-1(-/-)Apoe(-/-) and controls. In contrast, TIMP-1(-/-) Apoe(-/-) animals only had a significant reduction in vascular smooth muscle cell content compared with Apoe(-/-) controls. In vitro and in vivo findings implicated heightened monocyte/macrophage invasion in the detrimental effects observed on atherosclerotic plaque composition in TIMP-2(-/-) Apoe(-/-) mice. Moreover, TIMP-2 specifically decreased MMP-14-dependent monocyte/macrophage infiltration into sites of experimentally induced inflammation and established atherosclerotic lesions.
conclusionOur data demonstrate that TIMP-2 plays a greater protective role than TIMP-1 during the pathogenesis of atherosclerosis, in part by suppressing MMP-14-dependent monocyte/macrophage accumulation into plaques.
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Registered trials
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