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Dysfunctional bone marrow‐derived endothelial progenitor cells in chronic Ang II infusion rat model of hypertension
Author(s) -
Jun Joo Yun,
Zubcevic Jasenka,
Afzal Aqeela,
Carvajal Jessica Marulanda,
Shan Zhiying,
Mocco J,
Raizada Mohan K
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.878.7
Subject(s) - bone marrow , medicine , progenitor cell , endocrinology , angiotensin ii , endothelial progenitor cell , receptor , stem cell , biology , genetics
Bone marrow (BM)‐derived endothelial progenitor cell (EPC) contribute to the maintenance of vascular homeostasis and EPC dysfunction is implicated in the vascular pathophysiology in hypertension. Thus, we propose Angiotensin II (Ang II)‐induced neurogenic hypertension is associated with dysfunctional EPC and elevated inflammatory cells (ICs). Ang II infused SD rats (200ng/kg/min, SC, 4–12 weeks) were used to induce hypertension. CD90 + /CD4 − /5 − /8cells were isolated from femur and blood and their functions were assessed. BM and blood EPC decreased by 35% and 70% after 4 and 12 weeks of Ang II infusion, respectively. This was associated with significant increases in BM and blood IC (CD4 + /8 + /25 + , CD3 + /45 + ; CD68 + ) measured by FACS, leading to significant reduction in EPC/IC. BM EPC migration and proliferation ability toward SDF was reduced by 70±5% at 6 wks, 75±4% at 12 wks, and by 40±3% at 6 wks, 44±5% at 12 wks of Ang II infusion, respectively. Tube formation assay showed endothelial cells from Ang II rats decreased tube length (~25%) and branch numbers (~23%) compared to control. RT‐PCR also showed significant decrease in CXCR4 (~30%) and CXCL12 (~40%) mRNA from 12 weeks Ang II rats. In summary, these data demonstrate EPC/IC is significantly decreased as a result of decreased EPC/increased IC in Ang II induced hypertension. EPC from hypertensive rats are dysfunctional with decreased SDF‐1 and its receptor mRNA. HL33610