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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Animals, Animals, Newborn, Arteries, Body Weight, Hemodynamics, Hypertension, Pulmonary, Hypertrophy, Right Ventricular, Hypoxia, Lung, Matrix Metalloproteinase 9, Mice, Mice, Transgenic, Muscle, Smooth, Vascular, Myocardium, Organ Size, Plasminogen, Pulmonary Circulation, Receptors, Cell Surface, Receptors, Urokinase Plasminogen Activator, Tissue Plasminogen Activator, Urokinase-Type Plasminogen Activator.
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Does deficiency of urokinase-type plasminogen activator-mediated plasmin generation impair vascular remodeling during hypoxia-induced pulmonary hypertension in mice? Context: Chronic hypoxia results in the development of pulmonary hypertension and subsequent right heart failure. A role of the plasminogen system in the pathogenesis of pulmonary hypertension and pulmonary vascular remodeling has been suggested. Mice with targeted deficiency of the gene encoding tissue-type plasminogen activator (t-PA(-/-)), urokinase-type plasminogen activator (u-PA(-/-)), u-PA receptor (u-PAR(-/-)), or plasminogen (plg(-/-)) were subjected to hypoxic conditions. Hypoxia caused a significant 2.5-fold rise in right ventricular pressure in wild-type mice. Deficiency of u-PA or plasminogen prevented this increase in right ventricular pressure, t-PA(-/-) mice showed changes that were fully comparable with wild-type mice, and u-PAR(-/-) mice showed a partial response. Hypoxia induced an increase in smooth muscle cells within pulmonary arterial walls and a vascular rarefaction in the lungs of wild-type but not of u-PA(-/-) or plg(-/-) mice. Elastic lamina fragmentation, observed in hypoxic wild-type but not in u-PA or plasminogen-deficient mice, suggested that proliferation of vascular smooth muscle cells was dependent on u-PA-mediated elastic membrane degradation. Hypoxia-induced right ventricular remodeling in wild-type mice, characterized by cardiomyocyte hypertrophy and increased collagen contents, was not seen in u-PA(-/-) and plg(-/-) mice.
assistant
Loss of the u-PA or plasminogen gene protects against the development of hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling. These observations point to an essential role of u-PA-mediated plasmin generation in the adaptive response to chronic hypoxia and the occurrence of hypoxic pulmonary vascular disease. Final Decision: yes