Angiogenesis and Endothelial Cell Repair in Renal Disease and Allograft Rejection

Reinders, Marlies E.J.; Rabelink, Ton J.; Briscoe, David M.

doi:10.1681/asn.2005121250

Cited by 134 publications

(149 citation statements)

References 118 publications

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“…Interestingly, EPO independently leads to angiogenesis for new cell growth such as capillary formation from pre-existing vessels into an avascular area [11,46]. EPO has both a mitogenic and chemotactic effect that can lead to matrix metalloproteinase-2 production, cell proliferation, and new vessel formation [2,3].…”

Section: Cardiovascular-renal Protection Angiogenesis and Epomentioning

confidence: 99%

“…Other avenues of study are directed to the development of derivations of EPO to reduce erythropoietic activity and the potential associated vascular complications [30]. Yet, these lines of investigation are not without limitations, since chemical derivatives of EPO can become absent of clinical efficacy [2,3] as well as possibly loose the ability to promote sustainable cytoprotective effects, such as neurogenesis [80] and angiogenesis [11,46].…”

Section: Future Directions For Clinical Efficacy Safety and Toxicitmentioning

confidence: 99%

“…Other clinical randomized control studies in patients with mild anemia and severe or resistant congestive heart failure have demonstrated that EPO in combination with intravenous iron can lead to increased left ventricular ejection fraction and a reduction in hospitalization days by almost eighty percent. In addition to the correction of anemia, EPO can promote microvascular growth in the heart, suggesting that functional cardiac recovery with EPO may ensue also from the generation of new blood vessels [45].Interestingly, EPO independently leads to angiogenesis for new cell growth such as capillary formation from pre-existing vessels into an avascular area [11,46]. EPO has both a mitogenic and chemotactic effect that can lead to matrix metalloproteinase-2 production, cell proliferation, and new vessel formation [2,3].…”

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confidence: 99%

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Raves and risks for erythropoietin

Maiese

Chong²,

Shang³

2008

Cytokine & Growth Factor Reviews

125

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Global use of erythropoietin (EPO) continues to increase as a proven agent for the treatment of anemia. Yet, EPO is no longer believed to have exclusive biological activity in the hematopoietic system and is now considered applicable for a variety of disorders such as diabetes, Alzheimer's disease, and cardiovascular disease. Treatment with EPO is considered to be robust and can prevent metabolic compromise, neuronal and vascular degeneration, and inflammatory cell activation. On the converse side, observations that EPO administration is not without risk have fueled controversy. Here we present recent advances that have elucidated a number of novel cellular pathways governed by EPO to open new therapeutic avenues for this agent and avert its potential deleterious effects. Keywordsangiogenesis; cardiac; diabetes; erythropoietin; neurodegeneration Historical Background for ErythropoietinInitially termed "hemopoietine", erythropoietin (EPO) became evident as a factor that could stimulate new red blood cell development through the pioneering studies of Carnot and Deflandre in 1906 [1]. This team of investigators demonstrated that plasma removed from rabbits following a bleeding stimulus that was later injected into control untreated rabbits would lead to the development of immature red blood cells, or reticulocytosis. A number of other investigators followed these studies that demonstrated similar findings that plasma from animals that were bled would yield a significant reticulocytosis. Interestingly, more elegant experiments later demonstrated that a rise in hemoglobin levels with reticulocytosis occurred in parabiotic rats when only one partner was exposed to hypoxia, illustrating that depressed oxygen tensions could stimulate EPO production. Eventually, human EPO protein was purified that paved the way for the cloning of the EPO gene and the development of recombinant EPO for clinical use [2,3]. *Corresponding Author: Kenneth Maiese, MD, Department of Neurology, 8C-1 UHC, Wayne State University School of Medicine, 4201 St. Antoine, Detroit,; email: aa2088@wayne.edu, kmaiese@med.wayne.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The production and secretion of the mature EPO also relies upon the integrity of the N-and O-linked chains. The EPO gene is located on chromosome 7, exists as a single copy in a 5.4 kb region of the genomic DNA, and encodes a polypeptide chain containing 193 amino acids. During the production and secretion of EPO, a 166 amino acid peptide is initially generated following the cleavage of a 27 amino acid hydrophobic secretory leader ...

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Section: Cardiovascular-renal Protection Angiogenesis and Epomentioning

confidence: 99%

Section: Future Directions For Clinical Efficacy Safety and Toxicitmentioning

confidence: 99%

mentioning

confidence: 99%

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Raves and risks for erythropoietin

Maiese

Chong²,

Shang³

2008

Cytokine & Growth Factor Reviews

125

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“…In models of cerebral ischemia, EPO promotes factors for angiogenesis such as Tie-2 and Angiopoietin-2 that may assist with the restoration of cerebral blood flow to pre-ischemic levels . EPO controlled angiogenesis also may play a significant role during renal inflammation and prevention of allograft rejection (Reinders, et al, 2006). Yet, it is important to consider the inhibition of angiogenesis.…”

mentioning

confidence: 99%

“…Other avenues of study are directed to the development of derivations of EPO to reduce erythropoietic activity and the potential associated vascular complications (Montero, et al, 2007). Yet, these lines of investigation are not without limitations, since chemical derivatives of EPO can become absent of clinical efficacy as well as possibly loose the ability to promote sustainable cytoprotective effects, such as neurogenesis (Gonzalez, et al, 2007) and angiogenesis , Reinders, et al, 2006, Slevin, et al, 2006, Zhang and Ma, 2007. …”

mentioning

confidence: 99%

Erythropoietin and Oxidative Stress

Maiese

Chong

Hou

et al. 2008

CNR

110

113

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Unmitigated oxidative stress can lead to diminished cellular longevity, accelerated aging, and accumulated toxic effects for an organism. Current investigations further suggest the significant disadvantages that can occur with cellular oxidative stress that can lead to clinical disability in a number of disorders, such as myocardial infarction, dementia, stroke, and diabetes. New therapeutic strategies are therefore sought that can be directed toward ameliorating the toxic effects of oxidative stress. Here we discuss the exciting potential of the growth factor and cytokine erythropoietin for the treatment of diseases such as cardiac ischemia, vascular injury, neurodegeneration, and diabetes through the modulation of cellular oxidative stress. Erythropoietin controls a variety of signal transduction pathways during oxidative stress that can involve Janus-tyrosine kinase 2, protein kinase B, signal transducer and activator of transcription pathways, Wnt proteins, mammalian forkhead transcription factors, caspases, and nuclear factor κB. Yet, the biological effects of erythropoietin may not always be beneficial and may be poor tolerated in a number of clinical scenarios, necessitating further basic and clinical investigations that emphasize the elucidation of the signal transduction pathways controlled by erythropoietin to direct both successful and safe clinical care. KeywordsAlzheimer's disease; Akt; angiogenesis; apoptosis; cancer; cardiac; caspases; diabetes; endothelial; erythropoietin; forkhead; FoxO; GSK-3β; inflammation; mitochondria; NF-κB; renal; STATs; Wnt OXIDATIVE STRESSInitial work in pathways that can lead to oxidative stress by early investigators observed that increased metabolic rates could be detrimental to animals in an elevated oxygen environment. More current studies point to the potential aging mechanisms and accumulated toxic effects for an organism that are tied to oxidative stress (Maiese, et al., 2008a NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript in organisms, or at least the rate of oxygen consumption in organisms, has intrigued several investigators. Pearl proposed that increased exposure to oxygen through an increased metabolic rate could lead to a shortened life span (Pearl, 1928). Subsequent work by multiple investigators has furthered this hypothesis by demonstrating that increased metabolic rates could be detrimental to animals in an elevated oxygen environment . When one moves to more current work, oxygen free radicals and mitochondrial DNA mutations have become associated with oxidative stress injury, aging mechanisms, and accumulated toxicity for an organism (Yui and Matsuura, 2006).Oxygen free radicals can be generated in elevated quantities during the reduction of oxygen and subsequently lead to cell injury and apoptosis. Oxidative stress occurs as a result of the development of reactive oxygen species that consist of oxygen free radicals and other chemical entities. These agents can involve superoxide free radicals, hydrogen peroxide, sin...

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The effects of endothelial progenitor cells on rat atherosclerosis

Wang

et al. 2014

Biotech and App Biochem

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Atherosclerosis (AS) is a progressive disease characterized by endothelial injury and lipid aggregation in the arterial walls. Studies have reported that endothelial progenitor cells (EPCs) derived from the bone marrow (BM) might provide an endogenous repair mechanism by differentiating into endothelial cells to replace the dysfunctional endothelium. Our study aims to investigate the effect of EPCs derived from rat BM on AS. EPCs transduced by recombinant adeno-associated virus-green fluorescent protein (GFP) were transplanted into a rat AS model. After 2 months of transplantation, the localization of GFP-labeled cells, morphology, and lipid content in the aorta were examined. GFP-labeled EPCs were found in the endothelial monolayer of the artery vessel in the GFP/EPC group. Hematoxylin and eosin staining suggested that the lipid deposits in the aortic endothelium in the EPC/GFP group were less compared with those in the untreated group. Oil Red O staining of liver slices showed that lipid droplets were obviously decreased in the GFP/EPC group. The endothelial nitric oxide synthase and apolipoprotein E mRNA levels in the GFP/EPC group were significantly higher, but the intercellular cell adhesion molecule-1 mRNA level was significantly lower compared with the control group. The results suggest that EPCs derived from the BM can repair the injured endothelium and promote an atherosclerotic lesion regression. Therefore, EPCs may provide a useful tool for the treatment of AS.

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Angiogenesis and Endothelial Cell Repair in Renal Disease and Allograft Rejection

Abstract: This review discusses the concept that the turnover and replacement of endothelial cells is a major mechanism in the maintenance of vascular integrity within the kidney.

Cited by 134 publications

References 118 publications

Raves and risks for erythropoietin

Raves and risks for erythropoietin

Erythropoietin and Oxidative Stress

The effects of endothelial progenitor cells on rat atherosclerosis

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