ArticleAmerican journal of physiology. Heart and circulatory physiology2014
Cardiac aging is initiated by matrix metalloproteinase-9-mediated endothelial dysfunction.
Article in American journal of physiology. Heart and circulatory physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 61 citations in OpenAlex.
- MMP-9 Gene Ablation Preserves Ejection Fraction During "Single-Hit" Model of HFrEF.Biochemical genetics · 2026Article
- Glycobiology-driven therapeutic targeting of glycan-binding proteins: mechanisms, diseases, and clinical translation.Signal transduction and targeted therapy · 2026Review
- Multicellular senescence programs in the aged heart.Journal of molecular and cellular cardiology plus · 2026Review
- C-C Motif Chemokine Ligand 2 and Chemokine Receptor 2 in Cardiovascular and Neural Aging and Aging-Related Diseases.International journal of molecular sciences · 2024Review
- A Need to Preserve Ejection Fraction during Heart Failure.International journal of molecular sciences · 2024Review
- Aging in Ocular Blood Vessels: Molecular Insights and the Role of Oxidative Stress.Biomedicines · 2024Review
- The role of cardiac resident macrophage in cardiac aging.Aging cell · 2023Review
- Effects of Aging on Collagen in the Skeletal Muscle of Mice.International journal of molecular sciences · 2023Article
- The extracellular matrix mechanics in the vasculature.Nature cardiovascular research · 2023Review
- Aging microenvironment and antitumor immunity for geriatric oncology: the landscape and future implications.Journal of hematology & oncology · 2023Review
- Beyond Static Pipes: Mechanisms and In Vitro Models of Vascular Aging.Cold Spring Harbor perspectives in medicine · 2022Review
- Effect of genetic depletion of MMP-9 on neurological manifestations of hypertension-induced intracerebral hemorrhages in aged mice.GeroScience · 2021Article
- Ageing, sex, and cardioprotection.British journal of pharmacology · 2020Review
- Bearing My Heart: The Role of Extracellular Matrix on Cardiac Development, Homeostasis, and Injury Response.Frontiers in cell and developmental biology · 2020Review
- Role of Macrophages in Cardioprotection.International journal of molecular sciences · 2019Review
- Comparison of Biomechanical Properties and Microstructure of Trabeculae Carneae, Papillary Muscles, and Myocardium in the Human Heart.Journal of biomechanical engineering · 2019Article
- Extracellular matrix roles in cardiorenal fibrosis: Potential therapeutic targets for CVD and CKD in the elderly.Pharmacology & therapeutics · 2019Review
- The Mouse Heart Attack Research Tool 1.0 database.American journal of physiology. Heart and circulatory physiology · 2018Article
- Myocardial infarction remodeling that progresses to heart failure: a signaling misunderstanding.American journal of physiology. Heart and circulatory physiology · 2018Review
- Macrophage overexpression of matrix metalloproteinase-9 in aged mice improves diastolic physiology and cardiac wound healing after myocardial infarction.American journal of physiology. Heart and circulatory physiology · 2018Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Aging is linked to increased matrix metalloproteinase-9 (MMP-9) expression and extracellular matrix turnover, as well as a decline in function of the left ventricle (LV). Previously, we demonstrated that C57BL/6J wild-type (WT) mice > 18 mo of age show impaired diastolic function, which was attenuated by MMP-9 deletion. To evaluate mechanisms that initiate the development of cardiac dysfunction, we compared the LVs of 6-9- and 15-18-mo-old WT and MMP-9 null (Null) mice. All groups showed similar LV function by echocardiography, indicating that dysfunction had not yet developed in the older group. Myocyte nuclei numbers and cross-sectional areas increased in both WT and Null 15-18-mo mice compared with young controls, indicating myocyte hypertrophy. Myocyte hypertrophy leads to an increased oxygen demand, and both WT and Null 15-18-mo mice showed an increase in angiogenic signaling. Plasma proteomic profiling and LV analysis revealed a threefold increase in von Willebrand factor and fivefold increase in vascular endothelial growth factor in WT 15-18-mo mice, which were further elevated in Null mice. In contrast to the upregulation of angiogenic stimulating factors, actual LV vessel numbers increased only in the 15-18-mo Null LV. The 15-18-mo WT showed amplified expression of inflammatory genes related to angiogenesis, including C-C chemokine receptor (CCR)7, CCR10, interleukin (IL)-1f8, IL-13, and IL-20 (all, P < 0.05), and these increases were blunted by MMP-9 deletion (all, P < 0.05). To measure vascular permeability as an index of endothelial function, we injected mice with FITC-labeled dextran. The 15-18-mo WT LV showed increased vascular permeability compared with young WT controls and 15-18-mo Null mice. Combined, our findings revealed that MMP-9 deletion improves angiogenesis, attenuates inflammation, and prevents vascular leakiness in the setting of cardiac aging.
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Registered trials
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