ArticleProceedings of the National Academy of Sciences of the United States of America2008
Plasminogen mediates the atherogenic effects of macrophage-expressed urokinase and accelerates atherosclerosis in apoE-knockout mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Plasminogen as a ribonucleoprotein: regulatory small RNA cargo modulates fibrinolysis and inflammation.Blood · 2025Article
- Metabolic reaction fluxes as amplifiers and buffers of risk alleles for coronary artery disease.Molecular systems biology · 2025Article
- In-depth proteomic profiling identifies potentiation of the LPS response by 7-ketocholesterol.Journal of molecular and cellular cardiology plus · 2025Article
- Changes to Urinary Proteome in High-Fat-DietBiomolecules · 2022Article
- PAI-1: A Major Player in the Vascular Dysfunction in Obstructive Sleep Apnea?International journal of molecular sciences · 2022Review
- Plasminogen Deficiency Significantly Reduces Vascular Wall Disease in a Murine Model of Type IIa Hypercholesterolemia.Biomedicines · 2021Article
- Article
- Targeting PAI-1 in Cardiovascular Disease: Structural Insights Into PAI-1 Functionality and Inhibition.Frontiers in cardiovascular medicine · 2020Review
- TCRβ-expressing macrophages induced by a pathogenic murine malaria correlate with parasite burden and enhanced phagocytic activity.PloS one · 2018Article
- Physiology and pathophysiology of the plasminogen system in the kidney.Pflugers Archiv : European journal of physiology · 2017Review
- Plasminogen promotes cholesterol efflux by the ABCA1 pathway.JCI insight · 2017Article
- Enzymatically Modified Low-Density Lipoprotein Promotes Foam Cell Formation in Smooth Muscle Cells via Macropinocytosis and Enhances Receptor-Mediated Uptake of Oxidized Low-Density Lipoprotein.Arteriosclerosis, thrombosis, and vascular biology · 2016Article
- Reduction of mouse atherosclerosis by urokinase inhibition or with a limited-spectrum matrix metalloproteinase inhibitor.Cardiovascular research · 2015Article
- Article
- Plasmin promotes foam cell formation by increasing macrophage catabolism of aggregated low-density lipoprotein.Arteriosclerosis, thrombosis, and vascular biology · 2013Article
- Article
- Oxidized phospholipids are present on plasminogen, affect fibrinolysis, and increase following acute myocardial infarction.Journal of the American College of Cardiology · 2012Article
- The annexin A2/S100A10 system in health and disease: emerging paradigms.Journal of biomedicine & biotechnology · 2012Review
- Urokinase-type plasminogen activator deficiency in bone marrow-derived cells augments rupture of angiotensin II-induced abdominal aortic aneurysms.Arteriosclerosis, thrombosis, and vascular biology · 2011Article
- Mechanisms of urokinase plasminogen activator (uPA)-mediated atherosclerosis: role of the uPA receptor and S100A8/A9 proteins.The Journal of biological chemistry · 2011Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Urokinase-type plasminogen activator (uPA) is expressed at elevated levels in atherosclerotic human arteries, primarily in macrophages. Plasminogen (Plg), the primary physiologic substrate of uPA, is present at significant levels in blood and interstitial fluid. Both uPA and Plg have activities that could affect atherosclerosis progression. Moreover, correlations between increased Plg activation and accelerated atherosclerosis are reported in several human studies. However, a coherent picture of the role of the uPA/Plg system in atherogenesis has not yet emerged, with at least one animal study suggesting that Plg is atheroprotective. We used a transgenic mouse model of macrophage-targeted uPA overexpression in apolipoprotein E-deficient mice to investigate the roles of uPA and Plg in atherosclerosis. We found that macrophage-expressed uPA accelerated atherosclerotic plaque growth and promoted aortic root dilation through Plg-dependent pathways. These pathways appeared to affect lesion progression rather than initiation and to include actions that disproportionately increase lipid accumulation in the artery wall. In addition, loss of Plg was protective against atherosclerosis both in the presence and absence of uPA overexpression. Transgenic mice with macrophage-targeted uPA overexpression reveal atherogenic roles for both uPA and Plg and are a useful experimental setting for investigating the molecular mechanisms that underlie clinically established relationships between uPA expression, Plg activation, and atherosclerosis progression.
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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.