Abstract 3751: Selective Improvement of Renal Function in Renovascular Disease by Intra-Renal Infusion of Endothelial Progenitor Cells Restores Myocardial Microvascular Integrity

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Xiangyang Zhu ◽  
Jing Lin ◽  
Kyle Textor ◽  
Alejandro R Chade ◽  
James D Krier ◽  
...  
Keyword(s):  
Renal Function ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Volume Fraction ◽  
Plasma Renin ◽  
In Vivo Studies ◽  
Systemic Hypertension ◽  
Renovascular Disease ◽  
Endothelial Progenitor

Background : Renovascular disease (RVD) and impaired renal function are important risk factors for cardiac disease, but it remained unclear whether selective recovery of renal function can reverse cardiac dysfunction. Aims: This study tested the hypothesis that improvement in renal function using selective intra-renal administration of endothelial progenitor cells (EPC) in swine renovascular hypertension would improve myocardial microvascular (MV) integrity. Methods: The functions of the myocardial MV (response to IV adenosine) and the stenotic kidney of 7 pigs were assessed in-vivo using multi-detector CT after 6 weeks of RVD and hypertension. Autologous EPC expanded in culture were then infused (10x10 6 cells) intra-renally, and in vivo studies repeated 4 wks later. Six normal pigs served as controls. Results : Glomerular filtration rate was lower in RVD compared to normal (47.9±10.1 vs. 70.8±4.3 mL/min, p<0.05) and improved after EPC (to 62.7±1.5 mL/min, p=NS vs. normal), as did renal blood flow. Mean arterial pressure remained elevated after EPC (120.7±11 and 129.4±6 vs. 99.9±4.7 mmHg in normal, p<0.05), and plasma renin activity was unchanged. Myocardial MV permeability-surface area increased in RVD in response to adenosine (0.009±0.001 to 0.011±0.002 AU, p=0.01), while MV volume fraction decreased (4.3±0.8 to 2.7±0.6%, p=0.01), indicating impaired MV barrier function and integrity. Contrarily, both remained unchanged in response to adenosine 4 wks after EPC (0.01±0.002 to 0.01±0.002 AU, p=0.24, and 3.5±0.8 to 3.4±0.5%, p=0.46, respectively), as did normal MV. Conclusion : A single intra-renal infusion of EPC that improved renal function in experimental RVD also preserved remote myocardial MV function, despite sustained systemic hypertension. These findings underscore the cross talk between renal and cardiac function, and the potential of selective renal EPC intervention to preserve both the kidney and heart in RVD. Renal and myocardial microvascular function change in normal and RVD before and after EPC treatment

scholarly journals Endothelial Progenitor Cells Restore Renal Function in Chronic Experimental Renovascular Disease

Circulation ◽  
2009 ◽  
Vol 119 (4) ◽  
pp. 547-557 ◽  
Author(s):  
Alejandro R. Chade ◽  
Xiangyang Zhu ◽  
Ronit Lavi ◽  
James D. Krier ◽  
Sorin Pislaru ◽  
...  
Keyword(s):  
Renal Function ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Renovascular Disease ◽  
Endothelial Progenitor

scholarly journals In Vivo Serial MR Imaging of Magnetically Labeled Endothelial Progenitor Cells Homing to the Endothelium Injured Artery in Mice

PLoS ONE ◽  
2011 ◽  
Vol 6 (6) ◽  
pp. e20790 ◽  
Author(s):  
Jun Chen ◽  
Zhen-Yu Jia ◽  
Zhan-Long Ma ◽  
Yuan-Yuan Wang ◽  
Gao-Jun Teng
Keyword(s):  
Mr Imaging ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Endothelial Progenitor ◽  
Injured Artery

Abstract 3955: Chemokines Fused to a Fractalkine Backbone and a GPI-Anchor Attract Embryonic Endothelial Progenitor Cells to the Site of Ischemia

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Chiraz El-Aouni ◽  
Franziska Globisch ◽  
Achim Pfosser ◽  
Georg Stachel ◽  
Rabea Hinkel ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Adhesion Molecule ◽  
Capillary Density ◽  
Gpi Anchor ◽  
Endothelial Progenitor ◽  
Collateral Growth ◽  
Artificial Adhesion

Recruitment of endothelial progenitor cells to the sites of ischemia is a prerequisite for efficient therapeutic neovascularization via vasculogenesis. Chemokines play a major role in the homing of EPCs at the ischemic vasculature, a mechanism fading in chronic ischemia. To overcome this limitation, we constructed an artificial adhesion molecule consisting of a GPI-anchor, a fractalkine-backbone and an SDF-1 head (SDF-1-fra-GPI), which was applied for enhanced recruitment of embryonic EPCs (eEPCs: CXCR4++, Tie2++, Thrombomodulin++, CD34-, MHCI-, vWF inducible, eNOS inducible) in vitro and in vivo . Methods: In a flow chamber adhesion assay, Control plasmids (pcDNA or GPI-SDF-1 cDNA) were compared to the SDF-1-fra-GPI construct for eEPC recruitment 24h after liposomal transfection of rat endothelial cells. In vivo, in rabbits (n=5 per group) at day 7 (d7) after femoral artery excision, 1 mg of the SDF-1-fra-GPI or eGFP cDNA was transfected into the ischemic limb. At d9, ischemic hindlimbs were retroinfused with 5x10 6 eEPCs. Angiography was performed for collateral quantification and frame count score at d9 and d37 (% of d9), capillary density was assessed via PECAM-1-staining (capillaries/muscle fiber = c/mf). Results: In vitro, eEPC adhesion (16±12 cells/field) was increased to a higher extent by SDF-1-fra-GPI (79±13) than SDF1-GPI (54±8) or control vector (37±8). In vivo , eEPC adhesion in the ischemic hindlimb after SDF-1-fra-GPI transfection compared to mock transfection (30±3 vs. 9±1 cells/field). Whereas capillary density was unaffected (1.66±0.30 SDF-1-Fra-GPI vs. 1.56±0.29 eEPCs), collateral growth (152±10% SDF-1-fra-GPI vs. 124±13%) as well as perfusion score (198±17% SDF-1-fra-GPI vs.160±6% eEPCs) further increased after SDF-1-fra-GPI transfection (controls: 1.24±0.12 c/mf, collaterals 105±8%, perfusion score 112±11%). We conclude that recruitment of EPCs expressing CXCR4 (the SDF-1 receptor) may benefit from pre-treatment of the recipient vasculature with SDF-1-Fra-GPI, an artificial adhesion molecule. This approach might be valuable for enhancing EPC recruitment in the scenario of therapeutic neovascular-ization of chronic ischemic syndromes.

β2AR-dependent signaling contributes to in-vivo reendothelialization capacity of endothelial progenitor cells by shear stress

2020 ◽  
Vol 38 (1) ◽  
pp. 82-94 ◽  
Author(s):  
Qingsong Hu ◽  
Tao Zhang ◽  
Yan Li ◽  
Jianyi Feng ◽  
Ruqiong Nie ◽  
...  
Keyword(s):  
Shear Stress ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Endothelial Progenitor

Renal effects induced by prolonged mPGES1 inhibition

2014 ◽  
Vol 306 (1) ◽  
pp. F68-F74 ◽  
Author(s):  
Francisco Salazar ◽  
Michael L. Vazquez ◽  
Jaime L. Masferrer ◽  
Gabriel Mbalaviele ◽  
Maria T. Llinas ◽  
...  
Keyword(s):  
Renal Function ◽  
Plasma Renin ◽  
In Vivo Studies ◽  
Renal Effects ◽  
Excretory Function ◽  
Membrane Bound ◽  
Inflammatory Drugs ◽  
Chronically Instrumented Dogs

The importance of membrane-bound PGE synthase 1 (mPGES1) in the regulation of renal function has been examined in mPGES1-deficient mice or by evaluating changes in its expression. However, it is unknown whether prolonged mPGES1 inhibition induces significant changes of renal function when Na+ intake is normal or low. This study examined the renal effects elicited by a selective mPGES1 inhibitor (PF-458) during 7 days in conscious chronically instrumented dogs with normal Na+ intake (NSI) or low Na+ intake (LSI). Results obtained in both in vitro and in vivo studies have strongly suggested that PF-458 is a selective mPGES1 inhibitor. The administration of 2.4 mg·kg−1·day−1 PF-458 to dogs with LSI did not induce significant changes in renal blood flow (RBF) and glomerular filtration rate (GFR). A larger dose of PF-458 (9.6 mg·kg−1·day−1) reduced RBF ( P < 0.05) but not GFR in dogs with LSI and did not induce changes of renal hemodynamic in dogs with NSI. Both doses of PF-458 elicited a decrease ( P < 0.05) in PGE2 and an increase ( P < 0.05) in 6-keto-PGF1α. The administration of PF-458 did not induce significant changes in renal excretory function, plasma renin activity, and plasma aldosterone and thromboxane B2 concentrations in dogs with LSI or NSI. The results obtained suggest that mPGES1 is involved in the regulation of RBF when Na+ intake is low and that the renal effects elicited by mPGES1 inhibition are modulated by a compensatory increment in PGI2. These results may have some therapeutical implications since it has been shown that prolonged mPGES1 inhibition has lower renal effects than those elicited by nonsteroidal anti-inflammatory drugs or selective cyclooxygenase-2 inhibitors.

scholarly journals Oxidant Stress Impairs In Vivo Reendothelialization Capacity of Endothelial Progenitor Cells From Patients With Type 2 Diabetes Mellitus

Circulation ◽  
2007 ◽  
Vol 116 (2) ◽  
pp. 163-173 ◽  
Author(s):  
Sajoscha A. Sorrentino ◽  
Ferdinand H. Bahlmann ◽  
Christian Besler ◽  
Maja Müller ◽  
Svenja Schulz ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Oxidant Stress ◽  
Endothelial Progenitor

Human Cord Blood-Derived Endothelial Progenitor Cells Engraft Following In Utero Transplantation, Integrate into the Developing Cytoarchitecture and Contribute to Ongoing Vasculogenesis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3714-3714
Author(s):  
Joshua A. Wood ◽  
Evan Colletti ◽  
Laura E. Mead ◽  
David A. Ingram ◽  
Christopher D. Porada ◽  
...  
Keyword(s):  
Cord Blood ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Connexin 43 ◽  
Flow Cytometric Analysis ◽  
Specific Cell ◽  
Endothelial Progenitor ◽  
Human Cord Blood ◽  
Fetal Sheep

Abstract Endothelial progenitor cells (EPC), whether isolated from the bone marrow (BM), peripheral (PB), or cord blood (CB), represent a promising tool for the development of novel cell therapies. EPC have been shown to contribute to re-endothelialization and neovascularization of damaged tissue, and have been proposed to be some of the primary regulators of tissue regeneration in organs such as the liver. Many studies have looked at the role of EPC in vasculogenic processes, but very few, if any, have focused their efforts on determining the complete differentiative potential of EPC upon transplantation in an experimental model that permits the robust formation of donor-derived tissue-specific cells in the absence of selective pressure to drive differentiation towards a specific phenotype. To this end, CB-derived EPC were obtained as previously described (Ingram et al. Blood:104,2004), transduced with a retroviral vector expressing dsRed, and transplanted (Tx) into 55–60 days old fetal sheep recipients (n=8) at concentrations ranging from 0.5–1.5 × 106cells/fetus. Recipients were then evaluated at 85 days post-transplant for the presence of donor (human)-specific cell types using flow cytometry and confocal microscopy. Using these methods, we found that levels of EPC engraftment in liver, as detected by dsRed expression, correlated directly with the Tx cell dose. Furthermore co-localization of CD31 or vWF was found within the dsRed+ cells. In animals receiving lower cell doses, EPC engrafted throughout the liver at the overall level of 0.12±0.03%; this number doubled in animals that received 2.6 × 106cells. Importantly, there was a preferential distribution of EPC around the vessels, with the EPC comprising 10 to 25% of the cells located around the perivascular areas, with some contributing directly to the endothelial layer of these vessels. Furthermore, expression of Connexin-43 and 45 in engrafted EPC demonstrated that the EPC had not only engrafted, but had also functionally integrated into the developing blood vessels. In addition, co-expression of albumin and alpha-fetoprotein in some of the engrafted EPC suggests that some of these cells may also have contributed to cells with a hepatocyte-like phenotype. Flow cytometric analysis of BM and PB of the transplanted sheep demonstrated that EPC engrafted and proliferated in the BM, with cells expressing CD105 (6.2±2.2) and CD146 (0.6±0.1), and continued to circulate in the PB with cells positive for CD105 (1.4±0.4) and CD146 (0.9±0.2). Of interest is that a CD45 negative aminopeptidase N+ (APN/CD13) population was found in both BM (18±7) and PB (5.6±2). This is particularly interesting, since CD13/APN is a potent regulator of vascular endothelial morphogenesis during angiogenesis. In conclusion, CB derived EPC are able to engraft and proliferate in vivo, integrate into the developing cytoarchitecture, and establish a circulating EPC pool ensuring long-term contribution to ongoing vasculogenesis.

scholarly journals Effects of androgens on endothelial progenitor cells in vitro and in vivo

2009 ◽  
Vol 117 (10) ◽  
pp. 355-364 ◽  
Author(s):  
Gian Paolo Fadini ◽  
Mattia Albiero ◽  
Andrea Cignarella ◽  
Chiara Bolego ◽  
Christian Pinna ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Endothelial Progenitor Cell ◽  
Cell Biology ◽  
Progenitor Cell ◽  
Adult Males ◽  
Endothelial Progenitor ◽  
Healthy Human

The beneficial or detrimental effects of androgens on the cardiovascular system are debated. Endothelial progenitor cells are bone-marrow-derived cells involved in endothelial healing and angiogenesis, which promote cardiovascular health. Oestrogens are potent stimulators of endothelial progenitor cells, and previous findings have indicated that androgens may improve the biology of these cells as well. In the present study, we show that testosterone and its active metabolite dihydrotestosterone exert no effects on the expansion and function of late endothelial progenitors isolated from the peripheral blood of healthy human adult males, whereas they positively modulate early ‘monocytic’ endothelial progenitor cells. In parallel, we show that castration in rats is followed by a decrease in circulating endothelial progenitor cells, but that testosterone and dihydrotestosterone replacement fails to restore endothelial progenitor cells towards normal levels. This is associated with persistently low oestrogen levels after androgen replacement in castrated rats. In a sample of 62 healthy middle-aged men, we show that circulating endothelial progenitor cell levels are more directly associated with oestradiol, rather than with testosterone, concentrations. In conclusion, our results collectively demonstrate that androgens exert no direct effects on endothelial progenitor cell biology in vitro and in vivo.

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