ArticleJournal of the American Heart Association2015
Matrix metalloproteinase-2 negatively regulates cardiac secreted phospholipase A2 to modulate inflammation and fever.
Article in Journal of the American Heart Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Understanding of the characteristics of fibroblasts in ischemic cardiomyopathy using single-nucleus RNA sequencing.Scientific reports · 2025Article
- Human iPSC-based disease modeling studies identify a common mechanistic defect and potential therapies for AMD and related macular dystrophies.Developmental cell · 2024Article
- An integrated multi-omics analysis of the effects of the food processing-induced contaminant 2-monochloropropane-1,3-diol (2-MCPD) in rat heart.Archives of toxicology · 2024Article
- Low-grade inflammation is associated with a heterogeneous lipoprotein subclass profile in an apparently healthy population sample.Lipids in health and disease · 2023Article
- Cellular mechanisms and molecular pathways linking bitter taste receptor signalling to cardiac inflammation, oxidative stress, arrhythmia and contractile dysfunction in heart diseases.Inflammopharmacology · 2023Review
- Extracellular vesicle-mediated bidirectional communication between heart and other organs.American journal of physiology. Heart and circulatory physiology · 2022Review
- Bioreactors for Vocal Fold Tissue Engineering.Tissue engineering. Part B, Reviews · 2022Review
- Proteomic profiling of MIS-C patients indicates heterogeneity relating to interferon gamma dysregulation and vascular endothelial dysfunction.Nature communications · 2021Article
- A Metalloproteinase Induces an Inflammatory Response in Preadipocytes with the Activation of COX Signalling Pathways and Participation of Endogenous Phospholipases ABiomolecules · 2021Article
- Matrix Metalloproteinases and Arterial Hypertension: Role of Oxidative Stress and Nitric Oxide in Vascular Functional and Structural Alterations.Biomolecules · 2021Review
- Targeting MMP-Regulation of Inflammation to Increase Metabolic Tolerance to COVID-19 Pathologies: A Hypothesis.Biomolecules · 2021Article
- Hepatocardiac or Cardiohepatic Interaction: From Traditional Chinese Medicine to Western Medicine.Evidence-based complementary and alternative medicine : eCAM · 2021Review
- NECo: A node embedding algorithm for multiplex heterogeneous networks.Proceedings. IEEE International Conference on Bioinformatics and Biomedicine · 2020Article
- Comparative Serum Analyses Identify Cytokines and Hormones Commonly Dysregulated as Well as Implicated in Promoting Osteolysis in MMP-2-Deficient Mice and Children.Frontiers in physiology · 2020Article
- Destroy to Rebuild: The Connection Between Bone Tissue Remodeling and Matrix Metalloproteinases.Frontiers in physiology · 2020Review
- Levels of matrix metalloproteinase-2 in committed differentiation of bone marrow mesenchymal stem cells induced by kartogenin.The Journal of international medical research · 2019Article
- Emerging pathways of communication between the heart and non-cardiac organs.Journal of biomedical research · 2019Article
- Cardiomyokines from the heart.Cellular and molecular life sciences : CMLS · 2018Review
- The cre-inducer doxycycline lowers cytokine and chemokine transcript levels in the gut of mice.Journal of applied genetics · 2017Article
- Novel Role for Matrix Metalloproteinase 9 in Modulation of Cholesterol Metabolism.Journal of the American Heart Association · 2016Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundMatrix metalloproteinase (MMP)-2 deficiency makes humans and mice susceptible to inflammation. Here, we reveal an MMP-2-mediated mechanism that modulates the inflammatory response via secretory phospholipase A2 (sPLA2), a phospholipid hydrolase that releases fatty acids, including precursors of eicosanoids. METHODS AND
resultsMmp2(-/-) (and, to a lesser extent, Mmp7(-/-) and Mmp9(-/-)) mice had between 10- and 1000-fold elevated sPLA2 activity in plasma and heart, increased eicosanoids and inflammatory markers (both in the liver and heart), and exacerbated lipopolysaccharide-induced fever, all of which were blunted by adenovirus-mediated MMP-2 overexpression and varespladib (pharmacological sPLA2 inhibitor). Moreover, Mmp2 deficiency caused sPLA2-mediated dysregulation of cardiac lipid metabolic gene expression. Compared with liver, kidney, and skeletal muscle, the heart was the single major source of the Ca(2+)-dependent, ≈20-kDa, varespladib-inhibitable sPLA2 that circulates when MMP-2 is deficient. PLA2G5, which is a major cardiac sPLA2 isoform, was proinflammatory when Mmp2 was deficient. Treatment of wild-type (Mmp2(+/+)) mice with doxycycline (to inhibit MMP-2) recapitulated the Mmp2(-/-) phenotype of increased cardiac sPLA2 activity, prostaglandin E2 levels, and inflammatory gene expression. Treatment with either indomethacin (to inhibit cyclooxygenase-dependent eicosanoid production) or varespladib (which inhibited eicosanoid production) triggered acute hypertension in Mmp2(-/-) mice, revealing their reliance on eicosanoids for blood pressure homeostasis.
conclusionsA heart-centric MMP-2/sPLA2 axis may modulate blood pressure homeostasis, inflammatory and metabolic gene expression, and the severity of fever. This discovery helps researchers to understand the cardiovascular and systemic effects of MMP-2 inhibitors and suggests a disease mechanism for human MMP-2 gene deficiency.
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Registered trials
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