| First Author | Tannenberg P | Year | 2018 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 314 |
| Issue | 4 | Pages | L593-L605 |
| PubMed ID | 29212800 | Mgi Jnum | J:261009 |
| Mgi Id | MGI:6150792 | Doi | 10.1152/ajplung.00054.2017 |
| Citation | Tannenberg P, et al. (2018) Extracellular retention of PDGF-B directs vascular remodeling in mouse hypoxia-induced pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 314(4):L593-L605 |
| abstractText | 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. |
