Cell tracking suggests pathophysiological and therapeutic role of bone marrow cells in Sugen5416/hypoxia rat model of pulmonary arterial hypertension

2021 ◽  
Author(s):  
Hideki Miwa ◽  
Seiichiro Sakao ◽  
Takayuki Jujo Sanada ◽  
Hidemi Suzuki ◽  
Atsushi Hata ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Rat Model ◽  
Cell Tracking ◽  
Bone Marrow Cells ◽  
Therapeutic Role ◽  
Pulmonary Arterial ◽  
Marrow Cells

scholarly journals Silibinin Upregulates CXCR4 Expression in Cultured Bone Marrow Cells (BMCs) Especially in Pulmonary Arterial Hypertension Rat Model

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1276
Author(s):  
Tingting Zhang ◽  
Nanako Kawaguchi ◽  
Kunikazu Tsuji ◽  
Emiko Hayama ◽  
Yoshiyuki Furutani ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Bone Marrow Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Cxcr4 Expression ◽  
Hypoxic Conditions ◽  
Pulmonary Arterial ◽  
Marrow Cells

Previously we reported that silibinin ameliorated pulmonary arterial hypertension (PAH) in rat PAH models, possibly through the suppression of the CXCR4/SDF-1, until the point where PAH became a severe and irreversible condition. To further investigate how silibinin ameliorates PAH, we first attempted to clarify its effect on bone marrow cells (BMCs), since the CXCR4/SDF-1 axis is known to regulate stem cell migration and attachment in BM niches. Rat PAH models were established through a combination of a single subcutaneous injection of monocrotaline (MCT) and chronic hypoxic conditions (10% O2). BMCs were harvested and cultured, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and flow cytometry (FCM) were performed to investigate whether silibinin affected CXCR4 expression. Silibinin upregulated the gene expression of stem cell related markers CXCR4, SDF-1, SCF, and c-Kit, inflammatory markers IL-6 and TNFα, mesenchymal stem cell (MSC)-related markers CD44 and CD29, and the granulocyte/monocyte-macrophage marker CD14 in cultured BM in PAH rats, but not in normal rats, except CXCR4. FCM showed that silibinin increased the CXCR4-positive cell population in a granulocyte fraction of cultured BMCs. However, immunohistochemical (IHC) staining showed no significant change in CXCR4 expression in the BM of the tibias. These results suggest that silibinin increases the expression of CXCR4 in BM, and the increased CXCR4-positive cells could be granulocytes/monocyte-macrophages.

scholarly journals Serotonin 5-HT2B receptors are required for bone-marrow contribution to pulmonary arterial hypertension

Blood ◽  
2012 ◽  
Vol 119 (7) ◽  
pp. 1772-1780 ◽  
Author(s):  
Jean-Marie Launay ◽  
Philippe Hervé ◽  
Jacques Callebert ◽  
Ziad Mallat ◽  
Corinne Collet ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Progenitor Cells ◽  
Vascular Remodeling ◽  
Bone Marrow Cells ◽  
Ex Vivo ◽  
Differentiation Potential ◽  
Pulmonary Arterial ◽  
Marrow Cells

Abstract Pulmonary arterial hypertension (PAH) is a progressive disease characterized by lung endothelial dysfunction and vascular remodeling. Recently, bone marrow progenitor cells have been localized to PAH lungs, raising the question of their role in disease progression. Independently, serotonin (5-HT) and its receptors have been identified as contributors to the PAH pathogenesis. We hypothesized that 1 of these receptors, 5-HT2B, is involved in bone marrow stem cell mobilization that participates in the development of PAH and pulmonary vascular remodeling. A first study revealed expression of 5-HT2B receptors by circulating c-kit+ precursor cells, whereas mice lacking 5-HT2B receptors showed alterations in platelets and monocyte-macrophage numbers, and in myeloid lineages of bone marrow. Strikingly, mice with restricted expression of 5-HT2B receptors in bone marrow cells developed hypoxia or monocrotaline-induced increase in pulmonary pressure and vascular remodeling, whereas restricted elimination of 5-HT2B receptors on bone marrow cells confers a complete resistance. Moreover, ex vivo culture of human CD34+ or mice c-kit+ progenitor cells in the presence of a 5-HT2B receptor antagonist resulted in altered myeloid differentiation potential. Thus, we demonstrate that activation of 5-HT2B receptors on bone marrow lineage progenitors is critical for the development of PAH.

Abstract 18446: Identification of a Novel Cellular Actor Participating in Vascular Remodeling During Pulmonary Arterial Hypertension : the PW1+ Progenitor Cells

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
France Dierick
Keyword(s):  
Bone Marrow ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Vascular Remodeling ◽  
Bone Marrow Cells ◽  
Mouse Lung ◽  
Pulmonary Vessels ◽  
Pulmonary Arterial ◽  
Lung Vessels

AIM: PW1+ progenitors were identified in various adult tissues and can differentiate in smooth muscle cells (SMC) in vitro. Our hypothesis is that PW1+ progenitors are recruited to participate in the vascular remodeling during pulmonary arterial hypertension (PAH). METHODS: PW1IRESnLacZ+/- mice express the β-galactosidase as a reporter gene for PW1 expression allowing to follow the lineage of PW1+ cells during a few days. These mice were exposed to chronic hypoxia (CH) to induce PAH, lung vessels neomuscularisation and SMC proliferation. PW1+ and β-Gal+ cells were studied by FACS and by immunofluorescence. RESULTS: PW1+ cells are localized in the lung parenchyma and in the perivascular zone in rodent and human lung. Two PW1+ populations were identified by flow cytometry in the mouse lung 1/ a Sca-1high/CD34high/PDGFR-α+ population which differentiates into calponin+ or α-SMA+ SMC and into vWF+ endothelial cell and 2/ a CD34-/CD146+ population expressing pericyte markers. After 2-4 days of CH, the number of lung PW1+ cells is increased (x3.5, p<0.01) and, in small pulmonary vessels media, the proportion of β-Gal+ SMC derived from PW1+ cells is increased (64±6% vs 35±3%, p<0.05) suggesting a recruitment and differentiation of PW1+ cells into lung vascular SMC. Moreover WT mice irradiated and engrafted with GFP+/β-Gal+ bone marrow cells do not show any increase in GFP+ SMC in lung vessels and do not show any β-Gal+ cells in the lung indicating that the lung PW1+ progenitors are not derived from bone marrow . Moreover, in the human PAH lung, PW1+ cells were observed in remodeled vascular structures: in the media of remodeled vessel and in plexiform lesions. CONCLUSION: These results suggest that lung resident PW1+ progenitors are recruited to participate in the vascular remodeling of small pulmonary vessels in experimental and human PAH. These progenitors show characteristics of pericytes and of vascular progenitors.

Pathogenic and Therapeutic Role of MicroRNA in Pulmonary Arterial Hypertension

2017 ◽  
pp. 31-54 ◽  
Author(s):  
Aleksandra Babicheva ◽  
Kimberly M. McDermott ◽  
Samuel C. Williams ◽  
Allison M. Yee ◽  
Swetaleena Dash ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Therapeutic Role ◽  
Pulmonary Arterial

Navigating the Road to Transplant in Pulmonary Arterial Hypertension: A Road Less Taken

2016 ◽  
Vol 15 (1) ◽  
pp. 12-13
Author(s):  
Adaani E. Frost ◽  
Harrison W. Farber
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Lung Transplantation ◽  
Small Cell ◽  
Small Cell Lung ◽  
Donor Organ ◽  
The Road ◽  
Lung Allocation Score ◽  
Pulmonary Arterial

Dramatic advances in therapy for pulmonary arterial hypertension (PAH) in the last 20 years have improved survival from a median of 2.5 years in the pretreatment era to 7.5 years currently. However, impressive as that may seem, it is important to note that a median survival of 7.5 years is equivalent to that of surgically resected non-small cell lung cancer, thus underscoring the importance of lung transplantation as a treatment option in patients with PAH. In this edition of Advances, Edelman has reviewed the pathway to transplantation for patients with PAH, detailing the recommendations for timing of referral, listing for lung transplantation, the role of the lung allocation score in allocating a donor organ, and the outcome of lung transplantation.

An Expanding Role of Biomarkers in Pulmonary Arterial Hypertension

2017 ◽  
Vol 18 (6) ◽  
Author(s):  
Mustafa Yildiz ◽  
Alparslan Sahin ◽  
Michael Behnes ◽  
İbrahim Akin
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Pulmonary Arterial
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