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Rationale: Urokinase plasminogen activator (uPA) interacts with its receptor on inflammatory and migrating cells to regulate extracellular matrix degradation, cell adhesion, and inflammatory cell activation. It is necessary for the development of an appropriate immune response and is involved in tissue remodeling. The PLAU gene codes for this enzyme, and is located on 10q24. This region has demonstrated evidence for linkage in a genome scan for asthma in a sample from northeastern Quebec. Here, we hypothesized that uPA may function as a regulator of asthma susceptibility.
Objectives: To test for association between asthma and genetic variants of PLAU.
Methods: We sequenced PLAU and tested for genetic association between identified variants and asthma-related traits in a French-Canadian familial collection (231 families, 1,139 subjects). Additional association studies were performed in two other family-based Canadian cohorts (Canadian Asthma Primary Prevention Study [CAPPS], 238 trios; and Study of Asthma Genes and the Environment [SAGE], 237 trios).
Measurements And Main Results: In the original sample, under the dominant model, the common alleles, rs2227564C (P141) and rs2227566T, were associated with asthma (p = 0.011 and 0.045, respectively) and with airway hyperresponsiveness (AHR) (p = 0.026 and 0.038, respectively). Analysis of the linkage disequilibrium pattern also revealed association of the common haplotype for asthma, atopy, and AHR (p = 0.031, 0.043, and 0.006, respectively). Whereas no significant association was detected for PLAU single-nucleotide polymorphisms in the CAPPS cohort, association was observed in the SAGE cohort between the rs4065C allele and atopy under additive (p = 0.005) and dominant (p = 0.0001) genetic models.
Conclusions: This suggests a role for the uPA pathway in the pathogenesis of the disease.
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http://dx.doi.org/10.1164/rccm.200607-1012OC | DOI Listing |
Decidualization of endometrial stromal cells is a prerequisite for successful embryo implantation and early pregnancy. Decidualization dysregulation results in implantation failure. In our previous study, we reported that PAI-1 is abnormally downregulated in the endometrial tissue samples of patients with recurrent implantation failure.
View Article and Find Full Text PDFCatheter Cardiovasc Interv
December 2024
Department of Fetal, Neonatal and Cardiovascular Sciences, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Kawasaki Disease (KD) is a systemic vasculitis that can lead to coronary artery aneurysms (CAA) in up to 10% of treated cases, significantly increasing the risk of thrombosis and acute myocardial infarction (AMI). While thrombolytic therapy is commonly used in adult coronary syndromes, its application in pediatric KD remains poorly studied. We report a 9-month-old infant with KD and giant CAA complicated by a subocclusive thrombus in the left anterior descending artery (LAD).
View Article and Find Full Text PDFCureus
November 2024
Interventional Radiology, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, GBR.
Pulmonary embolism (PE) is the third most frequent cause of acute cardiovascular presentation after myocardial infarction and stroke. The treatment approach for PE consists of hemodynamic and respiratory support, anticoagulation, reperfusion treatment, and vena cava filters. Reperfusion treatment consists of systemic thrombolysis (recombinant tissue-type plasminogen activator, streptokinase, and urokinase); percutaneous catheter-directed therapy (CDT); and surgical embolectomy.
View Article and Find Full Text PDFJ Ethnopharmacol
December 2024
Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, China; Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, China; Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China; State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China. Electronic address:
Ethnopharmacological Relevance: Delayed tissue-type plasminogen activator (t-PA) thrombolysis, which has a restrictive therapeutic time window within 4.5 h following ischemic stroke (IS), increases the risk of hemorrhagic transformation (HT) and subsequent neurotoxicity. Studies have shown that the NLRP3 inflammasome activation reversely regulated by the PGC-1α leads to microglial polarization and pyroptosis to cause damage to nerve cells and the blood-brain barrier.
View Article and Find Full Text PDFBMC Cardiovasc Disord
December 2024
Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
Introduction: The activation of the plasmatic coagulation system is a significant contributor to acute myocardial infarction (AMI). This study aimed to investigate the association between the levels of tissue plasminogen activator-inhibitor complex (t-PAIC), thrombin-antithrombin complex (TAT), plasmin-α2 plasmin-inhibitor complex (PIC), and thrombomodulin (TM) with clinical outcomes in patients with AMI.
Methods: Blood samples were collected from 368 patients presenting with acute myocardial infarction in the emergency department to assess levels of t-PAIC, TAT, PIC, and TM.
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