IU Indianapolis ScholarWorks :: Browsing by Subject "Endothelial progenitor cells"

Browsing by Subject "Endothelial progenitor cells"

Now showing 1 - 9 of 9

Association Between Residential Greenness and Cardiovascular Disease Risk
(American Heart Association, 2018-12-18) Yeager, Ray; Riggs, Daniel W.; DeJarnett, Natasha; Tollerud, David J.; Wilson, Jeffrey S.; Conklin, Daniel J.; O'Toole, Timothy E.; McCracken, James; Lorkiewicz, Pawel; Xie, Zhengzhi; Zafar, Nagma; Krishnasamy, Sathya S.; Srivastava, Sanjay; Finch, Jordan; Keith, Rachel J.; DeFilippis, Andrew; Rai, Shesh N.; Liu, Gilbert; Bhatnagar, Aruni; Geography, School of Liberal Arts
Background Exposure to green vegetation has been linked to positive health, but the pathophysiological processes affected by exposure to vegetation remain unclear. To study the relationship between greenness and cardiovascular disease, we examined the association between residential greenness and biomarkers of cardiovascular injury and disease risk in susceptible individuals. Methods and Results In this cross-sectional study of 408 individuals recruited from a preventive cardiology clinic, we measured biomarkers of cardiovascular injury and risk in participant blood and urine. We estimated greenness from satellite-derived normalized difference vegetation index ( NDVI ) in zones with radii of 250 m and 1 km surrounding the participants' residences. We used generalized estimating equations to examine associations between greenness and cardiovascular disease biomarkers. We adjusted for residential clustering, demographic, clinical, and environmental variables. In fully adjusted models, contemporaneous NDVI within 250 m of participant residence was inversely associated with urinary levels of epinephrine (-6.9%; 95% confidence interval, -11.5, -2.0/0.1 NDVI ) and F2-isoprostane (-9.0%; 95% confidence interval, -15.1, -2.5/0.1 NDVI ). We found stronger associations between NDVI and urinary epinephrine in women, those not on β-blockers, and those who had not previously experienced a myocardial infarction. Of the 15 subtypes of circulating angiogenic cells examined, 11 were inversely associated (8.0-15.6% decrease/0.1 NDVI ), whereas 2 were positively associated (37.6-45.8% increase/0.1 NDVI ) with contemporaneous NDVI . Conclusions Independent of age, sex, race, smoking status, neighborhood deprivation, statin use, and roadway exposure, residential greenness is associated with lower levels of sympathetic activation, reduced oxidative stress, and higher angiogenic capacity.
Dysfunctional stem and progenitor cells impair fracture healing with age
(Baishideng Publishing Group, 2019-06-26) Wagner, Diane R.; Karnik, Sonali; Gunderson, Zachary J.; Nielsen, Jeffery J.; Fennimore, Alanna; Promer, Hunter J.; Lowery, Jonathan W.; Loghmani, M. Terry; Low, Philip S.; McKinley, Todd O.; Kacena, Melissa A.; Clauss, Matthias; Li, Jiliang; Orthopaedic Surgery, IU School of Medicine
Successful fracture healing requires the simultaneous regeneration of both the bone and vasculature; mesenchymal stem cells (MSCs) are directed to replace the bone tissue, while endothelial progenitor cells (EPCs) form the new vasculature that supplies blood to the fracture site. In the elderly, the healing process is slowed, partly due to decreased regenerative function of these stem and progenitor cells. MSCs from older individuals are impaired with regard to cell number, proliferative capacity, ability to migrate, and osteochondrogenic differentiation potential. The proliferation, migration and function of EPCs are also compromised with advanced age. Although the reasons for cellular dysfunction with age are complex and multidimensional, reduced expression of growth factors, accumulation of oxidative damage from reactive oxygen species, and altered signaling of the Sirtuin-1 pathway are contributing factors to aging at the cellular level of both MSCs and EPCs. Because of these geriatric-specific issues, effective treatment for fracture repair may require new therapeutic techniques to restore cellular function. Some suggested directions for potential treatments include cellular therapies, pharmacological agents, treatments targeting age-related molecular mechanisms, and physical therapeutics. Advanced age is the primary risk factor for a fracture, due to the low bone mass and inferior bone quality associated with aging; a better understanding of the dysfunctional behavior of the aging cell will provide a foundation for new treatments to decrease healing time and reduce the development of complications during the extended recovery from fracture healing in the elderly.
E2F1 Suppresses Oxidative Metabolism and Endothelial Differentiation of Bone Marrow Progenitor Cells
(American Heart Association, 2018-03-02) Xu, Shiyue; Tao, Jun; Yang, Liu; Zhang, Eric; Boriboun, Chan; Zhou, Junlan; Sun, Tianjiao; Cheng, Min; Huang, Kai; Shi, Jiawei; Dong, Nian-Guo; Liu, Qinghua; Zhao, Ting C.; Qiu, Hongyu; Harris, Robert A.; Chandel, Navdeep S.; Losordo, Douglas W.; Qin, Gangjian; Biochemistry and Molecular Biology, School of Medicine
RATIONALE: The majority of current cardiovascular cell therapy trials use bone marrow progenitor cells (BM PCs) and achieve only modest efficacy; the limited potential of these cells to differentiate into endothelial-lineage cells is one of the major barriers to the success of this promising therapy. We have previously reported that the E2F transcription factor 1 (E2F1) is a repressor of revascularization after ischemic injury. OBJECTIVE: We sought to define the role of E2F1 in the regulation of BM PC function. METHODS AND RESULTS: Ablation of E2F1 (E2F1 deficient) in mouse BM PCs increases oxidative metabolism and reduces lactate production, resulting in enhanced endothelial differentiation. The metabolic switch in E2F1-deficient BM PCs is mediated by a reduction in the expression of pyruvate dehydrogenase kinase 4 and pyruvate dehydrogenase kinase 2; overexpression of pyruvate dehydrogenase kinase 4 reverses the enhancement of oxidative metabolism and endothelial differentiation. Deletion of E2F1 in the BM increases the amount of PC-derived endothelial cells in the ischemic myocardium, enhances vascular growth, reduces infarct size, and improves cardiac function after myocardial infarction. CONCLUSION: Our results suggest a novel mechanism by which E2F1 mediates the metabolic control of BM PC differentiation, and strategies that inhibit E2F1 or enhance oxidative metabolism in BM PCs may improve the effectiveness of cell therapy.
Endothelial Colony Forming Cells (ECFCs): Identification, Specification and Modulation in Cardiovascular Diseases
(2009-12) Huang, Lan; Pescovitz, Mark D.; Quilliam, Lawrence A.; Ingram, David A., Jr.; Pescovitz, Mark D.
A hierarchy of endothelial colony forming cells (ECFCs) with different levels of proliferative potential has been identified in human circulating blood and blood vessels. High proliferative potential ECFCs (HPP-ECFCs) display properties (robust proliferative potential in vitro and vessel-forming ability in vivo) consistent with stem/progenitor cells for the endothelial lineage. Corneal endothelial cells (CECs) are different from circulating and resident vascular endothelial cells (ECs). Whereas systemic vascular endothelium slowly proliferates throughout life, CECs fail to proliferate in situ and merely expand in size to accommodate areas of CEC loss due to injury or senescence. However, we have identified an entire hierarchy of ECFC resident in bovine CECs. Thus, this study provides a new conceptual framework for defining corneal endothelial progenitor cell potential. The identification of persistent corneal HPP-ECFCs in adult subjects might contribute to regenerative medicine in corneal transplantation. While human cord blood derived ECFCs are able to form vessels in vivo, it is unknown whether they are committed to an arterial or venous fate. We have demonstrated that human cord blood derived ECFCs heterogeneously express gene transcripts normally restricted to arterial or venous endothelium. They can be induced to display an arterial gene expression pattern after vascular endothelial growth factor 165 (VEGF165) or Notch ligand Dll1 (Delta1ext-IgG) stimulation in vitro. However, the in vitro Dll1 primed ECFCs fail to display significant skewing toward arterial EC phenotype and function in vivo upon implantation, suggesting that in vitro priming is not sufficient for in vivo specification. Future studies will determine whether ECFCs are amenable to specification in vivo by altering the properties of the implantation microenvironment. There is emerging evidence suggesting that the concentration of circulating ECFCs is closely related to the adverse progression of cardiovascular disorders. In a pig model of acute myocardial ischemia (AMI), we have demonstrated that AMI rapidly mobilizes ECFCs into the circulation, with a significant shift toward HPP-ECFCs. The exact role of the mobilized HPP-ECFCs in homing and participation in repair of the ischemic tissue remains unknown. In summary, these studies contribute to an improved understanding of ECFCs and suggest several possible therapeutic applications of ECFCs.
In vitro effect of chlorambucil on human glioma cell lines (SF767 and U87-MG), and human microvascular endothelial cell (HMVEC) and endothelial progenitor cells (ECFCs), in the context of plasma chlorambucil concentrations in tumor-bearing dogs
(PLOS, 2018-09-07) Reese, Michael J.; Knapp, Deborah W.; Anderson, Kimberly M.; Mund, Julie A.; Case, Jamie; Jones, David R.; Packer, Rebecca A.; Medicine, School of Medicine
The objective of this study was to investigate a possible mechanism of action of metronomic chlorambucil on glioma by studying the in vitro cytotoxicity and anti-angiogenic effects on glioma and endothelial cells, respectively. The in vitro LD50 and IC50 of chlorambucil were determined using human SF767 and U87-MG glioma cell lines, human microvascular endothelial cells (HMVECs) and human endothelial colony forming cells (ECFCs). Results were analyzed in the context of chlorambucil concentrations measured in the plasma of tumor-bearing dogs receiving 4 mg m-2 metronomic chlorambucil. The LD50 and IC50 of chlorambucil were 270 μM and 114 μM for SF767, and 390 μM and 96 μM for U87-MG, respectively. The IC50 of chlorambucil was 0.53 μM and 145 μM for the HMVECs and ECFCs, respectively. In pharmacokinetic studies, the mean plasma Cmax of chlorambucil was 0.06 μM. Results suggest that metronomic chlorambucil in dogs does not achieve plasma concentrations high enough to cause direct cytotoxic or growth inhibitory effects on either glioma or endothelial cells.
Influence of the oxygen microenvironment on the proangiogenic potential of human endothelial colony forming cells
(Springer, 2009-06-21) Decaris, Martin L.; Lee, Chang I.; Yoder, Mervin C.; Tarantal, Alice F.; Leach, J. Kent; Pediatrics, School of Medicine
Therapeutic angiogenesis is a promising strategy to promote the formation of new or collateral vessels for tissue regeneration and repair. Since changes in tissue oxygen concentrations are known to stimulate numerous cell functions, these studies have focused on the oxygen microenvironment and its role on the angiogenic potential of endothelial cells. We analyzed the proangiogenic potential of human endothelial colony-forming cells (hECFCs), a highly proliferative population of circulating endothelial progenitor cells, and compared outcomes to human dermal microvascular cells (HMVECs) under oxygen tensions ranging from 1% to 21% O2, representative of ischemic or healthy tissues and standard culture conditions. Compared to HMVECs, hECFCs (1) exhibited significantly greater proliferation in both ischemic conditions and ambient air; (2) demonstrated increased migration compared to HMVECs when exposed to chemotactic gradients in reduced oxygen; and (3) exhibited comparable or superior proangiogenic potential in reduced oxygen conditions when assessed using a vessel-forming assay. These data demonstrate that the angiogenic potential of both endothelial populations is influenced by the local oxygen microenvironment. However, hECFCs exhibit a robust angiogenic potential in oxygen conditions representative of physiologic, ischemic, or ambient air conditions, and these findings suggest that hECFCs may be a superior cell source for use in cell-based approaches for the neovascularization of ischemic or engineered tissues.
N-acetylcysteine differentially regulates the populations of bone marrow and circulating endothelial progenitor cells in mice with limb ischemia
(Elsevier, 2020-08-15) Cui, Yuqi; Liu, Lingjuan; Xiao, Yuan; Li, Xin; Zhang, Jia; Xie, Xiaoyun; Tian, Jie; Sen, Chandan K.; He, Xiaoming; Hao, Hong; Liu, Zhenguo; Surgery, School of Medicine
Endothelial progenitor cells (EPCs) are important to tissue repair and regeneration especially after ischemic injury, and very heterogeneous in phenotypes and biological features. Reactive oxygen species are involved in regulating EPC number and function. N-acetylcysteine (NAC) inhibits ischemia-induced reactive oxygen species formation and promotes ischemic limb recovery. This study was to evaluate the effect of NAC on EPC subpopulations in bone marrow (BM) and blood in mice with limb ischemia. Limb ischemia was induced by femoral artery ligation in male C57BL/6 mice with or without NAC treatment. EPC subpopulations, intracellular reactive oxygen species production, cell proliferation and apoptosis in BM and blood cells were analyzed at baseline, day 3 (acute ischemia) and 21 (chronic) after ligation. c-Kit+/CD31+, Sca-1+/Flk-1+, CD34+/CD133+, and CD34+/Flk-1+ were used to define EPC subpopulations. Limb blood flow, function, muscle structure, and capillary density were evaluated with laser Doppler perfusion imaging, treadmill test, and immunohistochemistry, respectively, at day 3, 7, 14 and 21 post ischemia. Reactive oxygen species production in circulating and BM mononuclear cells and EPCs populations were significantly increased in BM and blood in mice with acute and chronic ischemia. NAC treatment effectively blocked ischemia-induced reactive oxygen species production in circulating and BM mononuclear cells, and selectively increased EPC population in circulation, not BM, with preserved proliferation in mice with chronic ischemia, and enhanced limb blood flow and function recovery, while preventing acute ischemia-induced increase in BM and circulating EPCs. These data demonstrated that NAC selectively enhanced circulating EPC population in mice with chronic limb ischemia.
Promoting vascular repair in the retina: can stem/progenitor cells help?
(Dovepress, 2016-05-26) Phuong Trinh, Thao Le; Calzi, Sergio Li; Shaw, Lynn C.; Yoder, Mervin C.; Grant, Maria B.; Biochemistry and Molecular Biology, School of Medicine
Since its first epidemic in the 1940s, retinopathy of prematurity (ROP) has been a challenging illness in neonatology. Higher than physiological oxygen levels impede the development of the immature retinal neuropil and vasculature. Current treatment regimens include cryotherapy, laser photocoagulation, and anti-VEGF agents. Unfortunately, none of these approaches can rescue the normal retinal vasculature, and each has significant safety concerns. The limitations of these approaches have led to new efforts to understand the pathological characteristics in each phase of ROP and to find a safer and more effective therapeutic approach. In the era of stem cell biology and with the need for new treatments for ROP, this review discusses the possible future use of unique populations of proangiogenic cells for therapeutic revascularization of the preterm retina.
Sleep-disordered breathing is associated with depletion of circulating endothelial progenitor cells and elevation in pulmonary arterial pressure in patients with decompensated systolic heart failure
(SciencePress, 2015-07) Zhang, Han; Feng, Liu; Wan, Qi-Lin; Hong, Yan; Li, Yan-Ming; Cheng, Guan-Chang; Han, Xin-Qiang; Department of Medicine, IU School of Medicine
BACKGROUND: Sleep-disordered breathing (SDB) is known to occur frequently in and may predict worsening progression of patients with congestive heart failure (CHF). SDB is also known to play an important role in the development of idiopathic pulmonary arterial hypertension (PAH) via inducing endothelial dysfunction and vascular remodeling, a pathological process that can be significantly influenced by factors such as osteoprotegerin (OPG) and endothelial progenitor cells (EPCs). The objective of this study is to determine if CHF with SDB is associated with changes in OPG, EPCs, and PAH. METHODS: EPCs were isolated, cultured, and quantified from CHF patients with SDB (n = 52), or without SDB (n = 68). OPG and N-terminal pro-brain natriuretic peptide (NT-proBNP) from each group was analyzed and correlated with EPCs and the mean pulmonary artery pressure (mPAP) measured by right heart catheterization. RESULTS: A significant decrease in circulating EPCs (29.30 ± 9.01 vs. 45.17 ± 10.51 EPCs/× 200 field; P < 0.05) was found in CHF patients with SDB compared to those without SDB. Both OPG (789.83 ± 89.38 vs. 551.29 ± 42.12 pg/mL; P < 0.05) and NT-proBNP (5946.50 ± 1434.50 vs. 3028.60 ± 811.90 ng/mL; P < 0.05) were also significantly elevated in SDB CHF patients who also had significantly elevated mPAP (50.2 ± 9.5 vs. 36.4 ± 4.1 mm Hg; P < 0.05). EPC numbers correlated inversely with the episodes of apnea and hypopnea per hour (RDI, r = -0.45, P = 0.037) and blood level of OPG (r = -0.53, P = 0.011). Although NT-proBNP was also increased significantly in patients with SDB, it had no correlation with either EPCs or RDI. CONCLUSIONS: SDB due to hypoxemia from decompensated CHF is associated with (1) OPG elevation, (2) EPC depletion, and (3) mPAP elevation. The inverse relationship of circulating OPG with EPCs suggests a likely mechanism for hypoxemia and OPG in the development of pulmonary vascular dysfunction via depleting EPCs, thus worsening prognosis of CHF.

Browsing by Subject "Endothelial progenitor cells"

Results Per Page

Sort Options