Abstract: FR-PO337
New Myeloid-Derived Cells Attributing to Cardio-Renal Syndrome
Session Information
- Hypertension and CVD: Mechanisms - I
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- Sagara, Akihiro, Kanazawa University Hospital, Kanazawa, Japan
- Sakai, Norihiko, Kanazawa University Hospital, Kanazawa, Japan
- Iwata, Yasunori, Kanazawa University Hospital, Kanazawa, Japan
- Furuichi, Kengo, Kanazawa University Hospital, Kanazawa, Japan
- Yamamoto, Yasuhiko, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
- Wada, Takashi, Kanazawa University Hospital, Kanazawa, Japan
Background
Cardiovascular disease is connected to chronic kidney disease (CKD), which is well-known as cardio-renal syndrome (CRS). Dysregulation of tissue repair is a pathological process leading to the end stage of organ failure characterized by tissue fibrosis. However, it remains unknown how fibrosis occurs in CRS under CKD.
Methods
To identify bone marrow (BM)-derived cells responsible for the development of CRS, continuous angiotensin II (AII) infusion plus unilateral ureteral obstruction (UUO) (AII+UUO) CRS model was employed using CAG-GFP mice and Col1a2 (Col)-GFP mice, with procedures of parabiosis and bone-marrow transplantation. Flow cytometry was used to identify recruited and migrated cells into the hearts or kidneys and gene expression analyses were followed by cell sorting. We also used immunohistochemistry and co-culture system of sorted cells with mouse embryonic fibroblasts (MEFs) from Col-Luciferase mice.
Results
We newly identified a cluster of myeloid cells, CD45+Sca1+ cells, in the hearts as well as kidneys of the CRS model. The cell type was a globular and mononuclear and this population was significantly increased in number along with the exacerbation of fibrosis. The CD45+Sca1+ cells had an activating potential for collagen production of the cultured MEFs and an ability of producing type 1 collagen by themselves. GeneChip analyses and flow cytometry showed the subpopulation of the CD45+Sca1+ cells, which expressed CCR8.
Conclusion
We could find a new population of myeloid-derived fibrosis-inducing cells, which were associated with cardiac and kidney fibrosis using our CRS model. Further studies are needed to elucidate the full role of this cell population in CRS under CKD.
Funding
- Government Support - Non-U.S.