Mice deficient in galectin-1 exhibit attenuated physiological responses to chronic hypoxia-induced pulmonary hypertension
| Autor: | Edward C. Dempsey, David Irwin, Charles Ivester, Moira Hagen, Katharine A Young, Joseph T. Crossno, David Case, Julie W. Harral, Susan M. Majka, Kenneth G. Morris, Françoise Poirier, Masatoshi Imamura, Michelle Carr, Mark Roedersheimer, James West, Abby Patterson, Milene Saavedra |
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| Přispěvatelé: | University of Colorado HSC Medicine, University of Colorado [Denver], Medicine, University of Colorado, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), American Heart Association Grant SDG-0335052N, the American Physiological Society Giles Filley Award, and National Institute of Diabetes and Digestive and Kidney Diseases Grant 5 T32 DK-007496, Ligue contre le Cancer, Comité de Paris, and ARC Foundations, National Heart, Lung, and Blood Institute Grants R01 HL-71596-01A1 and K08-HL-74512, and American Heart Association Grant 0575003N |
| Rok vydání: | 2007 |
| Předmět: |
Pathology
Galectin 1 Physiology MESH: Vascular Resistance MESH: Anoxia MESH: Base Sequence MESH: Mice Knockout [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract Muscle Smooth Vascular Pathogenesis Extracellular matrix Mice MESH: Microcirculation MESH: Animals Hypoxia Lung Mice Knockout 0303 health sciences 030302 biochemistry & molecular biology MESH: Muscle Smooth Vascular Extracellular Matrix Ventricular pressure medicine.symptom MESH: DNA Primers Pulmonary and Respiratory Medicine medicine.medical_specialty Hypertension Pulmonary MESH: Sheep In Vitro Techniques MESH: Extracellular Matrix Biology 03 medical and health sciences In vivo Physiology (medical) Internal medicine medicine Animals MESH: Lung MESH: Mice DNA Primers 030304 developmental biology MESH: Galectin 1 Sheep Base Sequence MESH: Hypertension Pulmonary Microcirculation MESH: Chronic Disease Mesenchymal Stem Cells Cell Biology Hypoxia (medical) medicine.disease Pulmonary hypertension MESH: Mesenchymal Stem Cells Endocrinology Apoptosis Chronic Disease Vascular Resistance Vasoconstriction |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, 2007, 292 (1), pp.L154-64. ⟨10.1152/ajplung.00192.2006⟩ |
| ISSN: | 1522-1504 1040-0605 |
| Popis: | Pulmonary hypertension (PH) is characterized by sustained vasoconstriction, with subsequent extracellular matrix (ECM) production and smooth muscle cell (SMC) proliferation. Changes in the ECM can modulate vasoreactivity and SMC contraction. Galectin-1 (Gal-1) is a hypoxia-inducible β-galactoside-binding lectin produced by vascular, interstitial, epithelial, and immune cells. Gal-1 regulates SMC differentiation, proliferation, and apoptosis via interactions with the ECM, as well as immune system function, and, therefore, likely plays a role in the pathogenesis of PH. We investigated the effects of Gal-1 during hypoxic PH by quantifying 1) Gal-1 expression in response to hypoxia in vitro and in vivo and 2) the effect of Gal-1 gene deletion on the magnitude of the PH response to chronic hypoxia in vivo. By constructing and screening a subtractive library, we found that acute hypoxia increases expression of Gal-1 mRNA in isolated pulmonary mesenchymal cells. In wild-type (WT) mice, Gal-1 immunoreactivity increased after 6 wk of hypoxia. Increased expression of Gal-1 protein was confirmed by quantitative Western analysis. Gal-1 knockout (Gal-1−/−) mice showed a decreased PH response, as measured by right ventricular pressure and the ratio of right ventricular to left ventricular + septum wet weight compared with their WT counterparts. However, the number and degree of muscularized vessels increased similarly in WT and Gal-1−/−mice. In response to chronic hypoxia, the decrease in factor 8-positive microvessel density was similar in both groups. Vasoreactivity of WT and Gal-1−/−mice was tested in vivo and with use of isolated perfused lungs exposed to acute hypoxia. Acute hypoxia caused a significant increase in RV pressure in wild-type and Gal-1−/−mice; however, the response of the Gal-1−/−mice was greater. These results suggest that Gal-1 influences the contractile response to hypoxia and subsequent remodeling during hypoxia-induced PH, which influences disease progression. |
| Databáze: | OpenAIRE |
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