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      Possible mechanism underlying the association between height and vascular remodeling in elderly Japanese men

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          Abstract

          Height is reported to be inversely associated with cardiovascular disease. And platelets play an important role in vascular remodeling by supporting CD34-positive cells. To clarify the association between height and platelet, we conducted a cross-sectional study of 219 elderly Japanese men. Since hemoglobin concentration is influenced by vascular remodeling activity, an analysis stratified by hemoglobin level was performed. An inverse association was seen between height and platelet count in subjects with a high hemoglobin concentration (≥ 14.5 g/dL), but not in subjects with a low hemoglobin concentration (< 14.5 g/dL). The standardized parameter estimates (β) were β = −0.22, p = 0.019 for subjects with high hemoglobin, and β = −0.01, p = 0.931 for subjects with low hemoglobin. We also found a positive association between platelets and carotid intima media thickness (CIMT) and circulating CD34-positive cells in subjects with high hemoglobin (partial correlation coefficient (r) = 0.21, p = 0.037 and r = 0.40, p =< 0.001), but not in subjects with low hemoglobin ( r = 0.04, p = 0.710 and r = 0.06, p = 0.544). In subjects with a high hemoglobin concentration, platelets were inversely associated with height, and positively associated with CIMT and circulating CD34-positive cells. These results indicate that subjects with a short stature activate vascular remodeling to a much greater extent than subjects with a tall stature.

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          Most cited references29

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          Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization.

          Endothelial progenitor cells (EPCs) have been isolated from circulating mononuclear cells in human peripheral blood and shown to be incorporated into foci of neovascularization, consistent with postnatal vasculogenesis. We determined whether endogenous stimuli (tissue ischemia) and exogenous cytokine therapy (granulocyte macrophage-colony stimulating factor, GM-CSF) mobilize EPCs and thereby contribute to neovascularization of ischemic tissues. The development of regional ischemia in both mice and rabbits increased the frequency of circulating EPCs. In mice, the effect of ischemia-induced EPC mobilization was demonstrated by enhanced ocular neovascularization after cornea micropocket surgery in mice with hindlimb ischemia compared with that in non-ischemic control mice. In rabbits with hindlimb ischemia, circulating EPCs were further augmented after pretreatment with GM-CSF, with a corresponding improvement in hindlimb neovascularization. There was direct evidence that EPCs that contributed to enhanced corneal neovascularization were specifically mobilized from the bone marrow in response to ischemia and GM-CSF in mice transplanted with bone marrow from transgenic donors expressing beta-galactosidase transcriptionally regulated by the endothelial cell-specific Tie-2 promoter. These findings indicate that circulating EPCs are mobilized endogenously in response to tissue ischemia or exogenously by cytokine therapy and thereby augment neovascularization of ischemic tissues.
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            Evidence for circulating bone marrow-derived endothelial cells.

            It has been proposed that hematopoietic and endothelial cells are derived from a common cell, the hemangioblast. In this study, we demonstrate that a subset of CD34(+) cells have the capacity to differentiate into endothelial cells in vitro in the presence of basic fibroblast growth factor, insulin-like growth factor-1, and vascular endothelial growth factor. These differentiated endothelial cells are CD34(+), stain for von Willebrand factor (vWF), and incorporate acetylated low-density lipoprotein (LDL). This suggests the possible existence of a bone marrow-derived precursor endothelial cell. To demonstrate this phenomenon in vivo, we used a canine bone marrow transplantation model, in which the marrow cells from the donor and recipient are genetically distinct. Between 6 to 8 months after transplantation, a Dacron graft, made impervious to prevent capillary ingrowth from the surrounding perigraft tissue, was implanted in the descending thoracic aorta. After 12 weeks, the graft was retrieved, and cells with endothelial morphology were identified by silver nitrate staining. Using the di(CA)n and tetranucleotide (GAAA)n repeat polymorphisms to distinguish between the donor and recipient DNA, we observed that only donor alleles were detected in DNA from positively stained cells on the impervious Dacron graft. These results strongly suggest that a subset of CD34+ cells localized in the bone marrow can be mobilized to the peripheral circulation and can colonize endothelial flow surfaces of vascular prostheses.
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              The ISHAGE guidelines for CD34+ cell determination by flow cytometry. International Society of Hematotherapy and Graft Engineering.

              The increased use of Peripheral Blood Stem Cells (PBSC) to reconstitute hematopoiesis in autotransplant and, more recently, allotransplant settings has not been associated with a consensus means to quality control the PBSC product. Since the small population of cells that bear the CD34 antigen are thought to be responsible for multilineage engraftment, graft assessment by flow cytometric quantitation of CD34+ cells should provide a rapid, reliable, and reproducible assay. Unfortunately, although a number of flow cytometric assays for CD34 enumeration have been described, the lack of a standardized method has led to the generation of widely divergent data. Furthermore, none of these assays has been validated as to interlaboratory reproducibility and suitability for widespread clinical application. In early 1995, the International Society of Hematotherapy and Graft Engineering (ISHAGE) established a Stem Cell Enumeration Committee, the mandate of which was to validate a simple, rapid, and sensitive flow cytometric method to quantitate CD34+ cells in peripheral blood and apheresis products. We also sought to establish its utility on a variety of flow cytometers in clinical laboratories and its reproducibility between transplant centers. Here, we describe the four-parameter flow methodology adopted by ISHAGE for validation in a multicenter study in North America.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                30 January 2018
                23 December 2017
                : 9
                : 8
                : 7749-7757
                Affiliations
                1 Department of Community Medicine, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan
                2 Department of Cardiovascular Disease Prevention, Osaka Center for Cancer and Cardiovascular Disease Prevention, Osaka, Japan
                3 Department of Island and Community Medicine, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan
                Author notes
                Correspondence to: Yuji Shimizu, shimizuyuji@ 123456nagasaki-u.ac.jp
                Article
                23660
                10.18632/oncotarget.23660
                5814254
                ff06cf9d-b38c-4a4a-a7ce-7c0d30e04516
                Copyright: © 2018 Shimizu et al.

                This article is distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 29 September 2017
                : 30 October 2017
                Categories
                Research Paper: Gerotarget (Focus on Aging)

                Oncology & Radiotherapy
                platelets,height,vascular remodeling,cimt,cd34-positive cell,gerotarget
                Oncology & Radiotherapy
                platelets, height, vascular remodeling, cimt, cd34-positive cell, gerotarget

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