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1.
Figure 2

Figure 2. From: Progenitor cells in pulmonary vascular remodeling.

Hypothetical scheme illustrating the concept of the ‘vasculogenic zone’. This vascular mural zone at the border between the media and adventitia contains EPCs and probably also multipotent mesodermal stem cells. EPCs present in this zone are proposed to differentiate into endothelial cells and form capillary-like sprouts from the vascular wall, whereas, the multipotent mesodermal stem cells in this zone may serve as precursors of macrophages, fibroblasts, and SMC (Adapted from Zengin et al.)[14]

Michael E. Yeager, et al. Pulm Circ. 2011 Jan-Mar;1(1):3-16.
2.
Figure 3

Figure 3. From: Progenitor cells in pulmonary vascular remodeling.

Identification of increased markers of c-kit+ cells in the blood and pulmonary artery of chronically hypoxic animals. Increased numbers of c-kit+ cells are present in the blood of chronically hypoxic calves compared to controls. Immunohistochemistry (brown peroxidase signal) revealed greater number of c-kit+ cells (arrows) in the vessel wall of the distal PA from hypoxic animals compared to controls. The c-kit+ cells were localized, contiguous to, and within, the vasa vasorum in the adventia (Adapted from Davie et al.)[106]

Michael E. Yeager, et al. Pulm Circ. 2011 Jan-Mar;1(1):3-16.
3.
Figure 5

Figure 5. From: Progenitor cells in pulmonary vascular remodeling.

Hypoxia-induced pulmonary remodeling is characterized by monocyte/fibrocyte accumulation in the adventitia and media. (a) Sustained hypoxia induces a robust appearance of mononuclear CD45+ cells (indirectly labeled with red fluorochrome) in the pulmonary arterial adventitia (these lesions are marked by triple large arrowheads in the ‘Hypoxia’ columns). (b) A large proportion (around 40%) of the CD45 + leukocytic cells (red fluorescence) accumulating in the remodeled pulmonary arterial adventitia of hypoxic hypertensive calves co-express type 1 pro-collagen (green fluorescence), suggestive of a fibrocyte phenotype. Scale bars, 5 μm. (Adapted from: Frid et al.).[17]

Michael E. Yeager, et al. Pulm Circ. 2011 Jan-Mar;1(1):3-16.
4.
Figure 7

Figure 7. From: Progenitor cells in pulmonary vascular remodeling.

CD133 positive cells accumulate and proliferate in the pulmonary artery intima of PAH patients. Immunostaining with antibodies to smooth muscle actin (SMA) demonstrates the accumulation of mesenchymal cells in the intima (a) DAPI staining demonstrates total cell accumulation (b) CD133+ cells comprise a portion of the cells accumulating in the intima (c) Ki67 immunostaining on the same section, re-photographed, demonstrate that the majority of proliferating cells are CD133+ (d) High magnification views of (c) and (d) are shown in panels (e) and (f), respectively.

Michael E. Yeager, et al. Pulm Circ. 2011 Jan-Mar;1(1):3-16.
5.
Figure 1

Figure 1. From: Progenitor cells in pulmonary vascular remodeling.

Potential origins of fibroblasts / myofibroblasts in the vessel wall. Several potential origins for tissue myofi broblasts have been proposed: (1) In several organs, α-SMA-expressing myofi broblasts are believed to originate from tissue-resident fi broblasts; (2) In the vasculature, myofi broblasts may arise through de-differentiation of resident SMC; (3) Epithelial cells can give rise to fibroblasts / myofibroblasts in the lung and other organs through a process of endothelial-mesenchymal transdifferentiation (EMT); (4) In the lung, endothelial-to-mesenchymal (EnMT) transition may provide another mechanism to generate myofibroblasts; (5) In various fi brotic lesions in tissue injury/ repair processes, bone marrow-derived circulating progenitor cells are proposed, to contribute to the pool of myofibroblasts (Adapted from Hinz et al.)[8]

Michael E. Yeager, et al. Pulm Circ. 2011 Jan-Mar;1(1):3-16.
6.
Figure 4

Figure 4. From: Progenitor cells in pulmonary vascular remodeling.

Expansion of the vasa vasorum in hypoxic pulmonary hypertension. Increase in the density of vasa vasorum (arrows) in proximal (a) and distal (b) vessels from hypoxic animals, compared with proximal (c) and distal (d) vessels from normoxic animals. Vasa (arrows) in hypoxic proximal and distal arteries express platelet endothelial cell adhesion molecule (PECAM)-1 (e and f, respectively). Quantitative morphometric analysis demonstrated that the volume density (Vv) of the vasa vasorum is signifi cantly greater in the adventitia and media of the pulmonary arteries of chronically hypoxic animals, at every level along the longitudinal axis of the pulmonary circulation than in the controls. Monocytes (CD11b) appear preferentially next to the vasa (eNOS+cells) in hypoxic vessels

Michael E. Yeager, et al. Pulm Circ. 2011 Jan-Mar;1(1):3-16.
7.
Figure 6

Figure 6. From: Progenitor cells in pulmonary vascular remodeling.

Hypoxia promotes the emergence of cells co-expressing leukocytic (CD11b) and the myofi broblast marker α-SM-actin. (a) A robust influx of CD11b+ cells (red) in the PA adventitia of chronically hypoxic rats correlates with a significant number of α-SMA+ myofibroblasts in that region. A – Adventitia; M – Media. (b) Double-label immunofluorescent staining for CD11b (red) and α-SMA (green), followed by deconvolution confocal microscopy analysis of the ‘boxed’ area in A, demonstrate cells that co-express both markers (arrowheads), or express only one of the markers (α-SMA, single arrow or CD11b, triple arrows). (c) Significant numbers of α-SMA+ myofibroblasts (brown staining in the adventitia (labeled (‘A’)) are present in distal PAs of the chronically hypoxic calves. (d) Double-label immunofl uorescent staining, followed by deconvolution confocal microscopy, demonstrate that some of the α-SMA+ myofibroblasts (green) co-express a macrophage marker CD68 (red) (arrowheads). DAPI (blue) labels cell nuclei. M, media; A, adventitia. Scale bars: 50 μm (a, c); 5 μm (b, d). (Adapted from: Frid et al.)[17]

Michael E. Yeager, et al. Pulm Circ. 2011 Jan-Mar;1(1):3-16.

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