ArticleThe Journal of experimental medicine2012
ProNGF, a cytokine induced after myocardial infarction in humans, targets pericytes to promote microvascular damage and activation.
Article in The Journal of experimental medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 77 citations in OpenAlex.
- Proteolytic remodelling of the extracellular matrix by pericytes.The FEBS journal · 2026Review
- Neurotrophic Factors: Emerging Biology and Therapeutic Applications for Cardiovascular Diseases.Metabolites · 2026Review
- Hypertension-induced heart failure disrupts cardiac sympathetic innervation.American journal of physiology. Heart and circulatory physiology · 2024Article
- Repair of the Infarcted Heart: Cellular Effectors, Molecular Mechanisms and Therapeutic Opportunities.Circulation research · 2024Review
- The role of cardiac pericytes in health and disease: therapeutic targets for myocardial infarction.Nature reviews. Cardiology · 2024Review
- Review
- Cardiac Pericytes Acquire a Fibrogenic Phenotype and Contribute to Vascular Maturation After Myocardial Infarction.Circulation · 2023Article
- Partial Mural Cell Ablation Disrupts Coronary Vasculature Integrity and Induces Systolic Dysfunction.Journal of the American Heart Association · 2023Article
- Cardiac pericytes mediate the remodeling response to myocardial infarction.The Journal of clinical investigation · 2023Article
- Brain-Derived Neurotrophic Factor Precursor Contributes to a Proinflammatory Program in Monocytes/Macrophages After Acute Myocardial Infarction.Journal of the American Heart Association · 2023Article
- Mesenchymal "stem" cells, or facilitators for the development of regenerative macrophages? Pericytes at the interface of wound healing.Frontiers in cell and developmental biology · 2023Review
- Therapeutics That Promote Sympathetic Reinnervation Modulate the Inflammatory Response After Myocardial Infarction.JACC. Basic to translational science · 2022Article
- Myocardial oedema: pathophysiological basis and implications for the failing heart.ESC heart failure · 2022Review
- NGF-p75 signaling coordinates skeletal cell migration during bone repair.Science advances · 2022Article
- Validation of Specific and Reliable Genetic Tools to Identify, Label, and Target Cardiac Pericytes in Mice.Journal of the American Heart Association · 2022Article
- The Potential of Gamma Secretase as a Therapeutic Target for Cardiac Diseases.Journal of personalized medicine · 2021Review
- Do Neurotrophins Connect Neurological Disorders and Heart Diseases?Biomolecules · 2021Review
- Pleiotropic activity of nerve growth factor in regulating cardiac functions and counteracting pathogenesis.ESC heart failure · 2021Review
- Analyses of the pericyte transcriptome in ischemic skeletal muscles.Stem cell research & therapy · 2021Article
- A combined evolutionary and structural approach to disclose the primary structural determinants essential for proneurotrophins biological functions.Computational and structural biotechnology journal · 2021Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Treatment of acute cardiac ischemia focuses on reestablishment of blood flow in coronary arteries. However, impaired microvascular perfusion damages peri-infarct tissue, despite arterial patency. Identification of cytokines that induce microvascular dysfunction would provide new targets to limit microvascular damage. Pro-nerve growth factor (NGF), the precursor of NGF, is a well characterized cytokine in the brain induced by injury. ProNGF activates p75 neurotrophin receptor (p75(NTR)) and sortilin receptors to mediate proapoptotic responses. We describe induction of proNGF by cardiomyocytes, and p75(NTR) in human arterioles after fatal myocardial infarction, but not with unrelated pathologies. After mouse cardiac ischemia-reperfusion (I-R) injury, rapid up-regulation of proNGF by cardiomyocytes and p75(NTR) by microvascular pericytes is observed. To identify proNGF actions, we generated a mouse expressing a mutant Ngf allele with impaired processing of proNGF to mature NGF. The proNGF-expressing mouse exhibits cardiac microvascular endothelial activation, a decrease in pericyte process length, and increased vascular permeability, leading to lethal cardiomyopathy in adulthood. Deletion of p75(NTR) in proNGF-expressing mice rescues the phenotype, confirming the importance of p75(NTR)-expressing pericytes in the development of microvascular injury. Furthermore, deficiency in p75(NTR) limits infarct size after I-R. These studies identify novel, nonneuronal actions for proNGF and suggest that proNGF represents a new target to limit microvascular dysfunction.
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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.