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Extracellular reten...
Extracellular retention of PDGF-B directs vascular remodeling in mouse hypoxia-induced pulmonary hypertension
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- Tannenberg, Philip (författare)
- Karolinska Institute,Karolinska Institutet
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- Chang, Ya-Ting (författare)
- Karolinska Institute,Chang Gung Memorial Hospital
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- Muhl, Lars (författare)
- Karolinska Institute,Karolinska Institutet
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- Laviña, Bàrbara (författare)
- Uppsala University,Uppsala universitet,Vaskulärbiologi
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- Gladh, Hanna (författare)
- Karolinska Institute
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- Genove, Guillem (författare)
- Karolinska Institute,Karolinska Institutet
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- Betsholtz, Christer (författare)
- Uppsala University,Karolinska Institute,Karolinska Institutet,Uppsala universitet,Vaskulärbiologi,Karolinska Inst, Dept Med, Integrated Cardio Metab Ctr, Huddinge, Sweden
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- Folestad, Erika (författare)
- Karolinska Institute,Karolinska Institutet
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- Tran-Lundmark, Karin (författare)
- Karolinska Institute,Lund University,Lunds universitet,Karolinska Institutet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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(creator_code:org_t)
- AMER PHYSIOLOGICAL SOC, 2018
- 2018
- Engelska.
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Ingår i: American Journal of Physiology - Lung cellular and Molecular Physiology. - : AMER PHYSIOLOGICAL SOC. - 1040-0605 .- 1522-1504. ; 314:4, s. 1593-1605
- Relaterad länk:
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https://www.physiolo...
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http://dx.doi.org/10...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- Pulmonary hypertension (PH) is a lethal condition, and current vasodilator therapy has limited effect. Antiproliferative strategies targeting platelet-derived growth factor (PDGF) receptors, such as imatinib, have generated promising results in animal studies. Imatinib is, however, a nonspecific tyrosine kinase inhibitor and has in clinical studies caused unacceptable adverse events. Further studies are needed on the role of PDGF signaling in PH. Here, mice expressing a variant of PDGF-B with no retention motif (Pdgfb(ret/ret)), resulting in defective binding to extracellular matrix, were studied. Following 4 wk of hypoxia, right ventricular systolic pressure, right ventricular hypertrophy, and vascular remodeling were examined. Pdgfb(ret/ret) mice did not develop PH, as assessed by hemodynamic parameters. Hypoxia did, however, induce vascular remodeling in Pdgfb(ret/ret) mice; but unlike the situation in controls where the remodeling led to an increased concentric muscularization of arteries, the vascular remodeling in Pdgfb(ret/ret) mice was characterized by a diffuse muscularization, in which cells expressing smooth muscle cell markers were found in the interalveolar septa detached from the normally muscularized intra-acinar vessels. Additionally, fewer NG2-positive perivascular cells were found in Pdgfb(ret/ret) lungs, and mRNA analyses showed significantly increased levels of Il6 following hypoxia, a known promigratory factor for pericytes. No differences in proliferation were detected at 4 wk. This study emphasizes the importance of extracellular matrix-growth factor interactions and adds to previous knowledge of PDGF-B in PH pathobiology. In summary, Pdgfb(ret/ret) mice have unaltered hemodynamic parameters following chronic hypoxia, possibly secondary to a disorganized vascular muscularization.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- extracellular matrix
- growth factor
- PDGF
- pulmonary hypertension
- vascular remodeling
- Extracellular matrix
- Growth factor
- PDGF
- Pulmonary hypertension
- Vascular remodeling
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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