ArticleThe Journal of clinical investigation2000
Elastase and matrix metalloproteinase inhibitors induce regression, and tenascin-C antisense prevents progression, of vascular disease.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
73 citing papers in PubMed, 299 citations in OpenAlex.
- The emerging role of integrin signaling in pulmonary vascular disease.American journal of physiology. Lung cellular and molecular physiology · 2026Review
- Identification of NR4A2 as a Potential Predictive Biomarker for Atherosclerosis.Combinatorial chemistry & high throughput screening · 2026Article
- The immune system in cardiovascular diseases: from basic mechanisms to therapeutic implications.Signal transduction and targeted therapy · 2025Review
- Analysis of the molecular mechanisms of ulcerative colitis and atherosclerosis by microarray data.Scientific reports · 2025Article
- New Drugs and Therapies in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2023Review
- Tenascin-C as a noninvasive biomarker of coronary artery disease.Molecular biology reports · 2022Article
- An integrated proteomic and transcriptomic signature of the failing right ventricle in monocrotaline induced pulmonary arterial hypertension in male rats.Frontiers in physiology · 2022Article
- A Novel Protective Role for Matrix Metalloproteinase-8 in the Pulmonary Vasculature.American journal of respiratory and critical care medicine · 2021Article
- Observational
- Exploring the Pathogenesis of Psoriasis Complicated With AtherosclerosisFrontiers in immunology · 2021Article
- Novel Experimental Therapies for Treatment of Pulmonary Arterial Hypertension.Journal of experimental pharmacology · 2021Review
- Molecular and Mechanical Mechanisms Regulating Ductus Arteriosus Closure in Preterm Infants.Frontiers in pediatrics · 2020Review
- Relationship between matrix metalloproteinase-3 serum level and pulmonary artery systolic pressure in patients with rheumatoid arthritis.Heart and vessels · 2018Observational
- Mechanobiological Feedback in Pulmonary Vascular Disease.Frontiers in physiology · 2018Review
- The Role of Neutrophils and Neutrophil Elastase in Pulmonary Arterial Hypertension.Frontiers in medicine · 2018Review
- The emerging role of microRNAs in hypoxia-induced pulmonary hypertension.Sleep & breathing = Schlaf & Atmung · 2016Review
- Activation of AMPK Prevents Monocrotaline-Induced Extracellular Matrix Remodeling of Pulmonary Artery.Medical science monitor basic research · 2016Article
- Skin tissue repair: Matrix microenvironmental influences.Matrix biology : journal of the International Society for Matrix Biology · 2016Review
- Elafin in pulmonary arterial hypertension. Beyond targeting elastases.American journal of respiratory and critical care medicine · 2015Article
- Mitochondrial dynamics in pulmonary arterial hypertension.Journal of molecular medicine (Berlin, Germany) · 2015Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increased expression of the glycoprotein tenascin-C (TN) is associated with progression of clinical and experimental pulmonary hypertension. In cultured smooth muscle cells (SMCs) TN is induced by matrix metalloproteinases (MMPs) and amplifies the proliferative response to growth factors. Conversely, suppression of TN leads to SMC apoptosis. We now report that hypertrophied rat pulmonary arteries in organ culture, which progressively thicken in association with cell proliferation and matrix accumulation, can be made to regress by inhibiting either serine elastases or MMPs. This effect is associated with reduced TN, suppression of SMC proliferation, and induction of apoptosis. Selective repression of TN by transfecting pulmonary arteries with antisense/ribozyme constructs also induces SMC apoptosis and arrests progressive vascular thickening but fails to induce regression. This failure is related to concomitant expansion of a SMC population, which produces an alternative cell survival alpha(v)beta(3) ligand, osteopontin (OPN), in response to pro-proliferative cues provided by a proteolytic environment. OPN rescues MMP inhibitor-induced SMC apoptosis, and alpha(v)beta(3) blockade induces apoptosis in hypertrophied arteries. Our data suggest that proteinase inhibition is a novel strategy to induce regression of vascular disease because this overcomes the pluripotentiality of SMC-matrix survival interactions and induces coordinated apoptosis and resorption of matrix.
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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.