CD31+ Circulating Angiogenic Cell Number and Subtypes are Reduced in Individuals with Chronic Stroke

Author(s): Rian Q. Landers-Ramos*, Katherine I. Kim, Brent Hickey, Frederick M. Ivey, Charlene E. Hafer-Macko, Richard F. Macko, Alice S. Ryan, Steven J. Prior

Journal Name: Current Neurovascular Research

Volume 18 , Issue 1 , 2021


Become EABM
Become Reviewer
Call for Editor

Abstract:

Background and Purpose: Reduced number and function of CD31+ circulating angiogenic cells (CACs) may explain vascular complications associated with the chronic phase stroke. The purpose of this study was to quantify CD31+ CAC paracrine function, total number and number of various subtypes of CD31+ CACs in individuals with chronic stroke compared with controls.

Methods: Peripheral blood mononuclear cells were isolated from chronic stroke participants and controls. CD31+ cells were quantified by flow cytometry, as was co-expression of CD31 in combination with CD14, CD3, CD11b, or CD34. Immunomagnetically selected CD31+ cells were cultured, and conditioned medium was used in a capillary-like network assay.

Results: Significantly lower levels of CD31+ CACs were found in stroke participants compared with controls (-24%; P=0.04). Additionally, CD31+/CD14+, CD31+/CD11b+ and CD31+/CD3+ cells were significantly lower in the chronic stroke group compared with controls (-45%, P=0.02; -47%, P=0.02 and -32%, P=0.03, respectively). There was no group effect on CD31+ CAC conditioned media-mediated capillary-like network formation.

Conclusion: CD31+ CACs and subtypes may serve as potential therapeutic targets in chronic stroke recovery.

Keywords: Circulating angiogenic cells, CD31, chronic stroke, angiogenic T cell, paracrine, angiogenesis.

[1]
Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics- 2013 update: A report from the American Heart Association. Circulation 2013; 127(1): e6-e245.
[http://dx.doi.org/10.1161/CIR.0b013e31828124ad] [PMID: 23239837]
[2]
Ivey FM, Hafer-Macko CE, Ryan AS, Macko RF. Impaired leg vasodilatory function after stroke: Adaptations with treadmill exercise training. Stroke 2010; 41(12): 2913-7.
[http://dx.doi.org/10.1161/STROKEAHA.110.599977] [PMID: 20966405]
[3]
Prior SJ, McKenzie MJ, Joseph LJ, et al. Reduced skeletal muscle capillarization and glucose intolerance. Microcirculation 2009; 16(3): 203-12.
[http://dx.doi.org/10.1080/10739680802502423] [PMID: 19225985]
[4]
Hill JM, Zalos G, Halcox JPJ, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 2003; 348(7): 593-600.
[http://dx.doi.org/10.1056/NEJMoa022287] [PMID: 12584367]
[5]
Ziegelhoeffer T, Fernandez B, Kostin S, et al. Bone marrow-derived cells do not incorporate into the adult growing vasculature. Circ Res 2004; 94(2): 230-8.
[http://dx.doi.org/10.1161/01.RES.0000110419.50982.1C] [PMID: 14656934]
[6]
Kim MH, Guo L, Kim HS, Kim SW. Characteristics of circulating CD31(+) cells from patients with coronary artery disease. J Cell Mol Med 2014; 18(11): 2321-30.
[http://dx.doi.org/10.1111/jcmm.12370] [PMID: 25267411]
[7]
Kushner EJ, Weil BR, MacEneaney OJ, et al. Human aging and CD31+ T-cell number, migration, apoptotic susceptibility, and telomere length. J Appl Physiol (1985) 2010; 109(6): 1756-61.
[http://dx.doi.org/10.1152/japplphysiol.00601.2010] [PMID: 20864561]
[8]
Ross MD, Malone EM, Simpson R, et al. Lower resting and exercise-induced circulating angiogenic progenitors and angiogenic T cells in older men. Am J Physiol Heart Circ Physiol 2018; 314(3): H392-402.
[http://dx.doi.org/10.1152/ajpheart.00592.2017] [PMID: 29167123]
[9]
Landers-Ramos RQ, Sapp RM, VandeWater E, et al. Investigating the extremes of the continuum of paracrine functions in CD34-/CD31+ CACs across diverse populations. Am J Physiol Heart Circ Physiol 2017; 312(1): H162-72.
[http://dx.doi.org/10.1152/ajpheart.00342.2016] [PMID: 27793853]
[10]
Landers-Ramos RQ, Sapp RM, Jenkins NT, et al. Chronic endurance exercise affects paracrine action of CD31and CD34 cells on endothelial tube formation. Am J Physiol Heart Circ Physiol 2015; 309(3): 00123.
[http://dx.doi.org/10.1152/ajpheart.00123.2015] [PMID: 26055789]
[11]
Sobrino T, Hurtado O, Moro MÁ, et al. The increase of circulating endothelial progenitor cells after acute ischemic stroke is associated with good outcome. Stroke 2007; 38(10): 2759-64.
[http://dx.doi.org/10.1161/STROKEAHA.107.484386] [PMID: 17761925]
[12]
Yip HK, Chang LT, Chang WN, et al. Level and value of circulating endothelial progenitor cells in patients after acute ischemic stroke. Stroke 2008; 39(1): 69-74.
[http://dx.doi.org/10.1161/STROKEAHA.107.489401] [PMID: 18063830]
[13]
Chu K, Jung KH, Lee ST, et al. Circulating endothelial progenitor cells as a new marker of endothelial dysfunction or repair in acute stroke. Stroke 2008; 39(5): 1441-7.
[http://dx.doi.org/10.1161/STROKEAHA.107.499236] [PMID: 18356550]
[14]
Li YF, Ren LN, Guo G, et al. Endothelial progenitor cells in ischemic stroke: An exploration from hypothesis to therapy. J Hematol Oncol 2015; 8(33): 33.
[http://dx.doi.org/10.1186/s13045-015-0130-8] [PMID: 25888494]
[15]
Ge Y, Cheng S, Larson MG, et al. Circulating CD31+ leukocyte frequency is associated with cardiovascular risk factors. Atherosclerosis 2013; 229(1): 228-33.
[http://dx.doi.org/10.1016/j.atherosclerosis.2013.04.017] [PMID: 23701996]
[16]
Shih YT, Wang MC, Yang TL, et al. β(2)-Integrin and Notch-1 differentially regulate CD34(+)CD31(+) cell plasticity in vascular niches. Cardiovasc Res 2012; 96(2): 296-307.
[http://dx.doi.org/10.1093/cvr/cvs256] [PMID: 22865639]
[17]
Hur J, Yoon CH, Kim HS, et al. Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis. Arterioscler Thromb Vasc Biol 2004; 24(2): 288-93.
[http://dx.doi.org/10.1161/01.ATV.0000114236.77009.06] [PMID: 14699017]
[18]
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18(6): 499-502.
[http://dx.doi.org/10.1093/clinchem/18.6.499] [PMID: 4337382]
[19]
Landers-Ramos RQ, Blumenthal JB, Prior SJ. Serum IL-6 and sIL-6R in type 2 diabetes contribute to impaired capillary-like network formation. J Appl Physiol (1985) 2019; 127(2): 385-92.
[http://dx.doi.org/10.1152/japplphysiol.00002.2019] [PMID: 31219767]
[20]
Carpentier GG, Martinelli M, Courty J, Cascone I. Angiogenesis analyzer for image. 4th ImageJ User & Developer Conference Mondorf les Bains Oct 24, 2012 - Oct 26, 2012 2012. Available from: http://www.wikicfp.com/cfp/servlet/event.showcfp?eventid=22226
[21]
Landers-Ramos RQ, Corrigan KJ, Guth LM, et al. Short-term exercise training improves flow-mediated dilation and circulating angiogenic cell number in older sedentary adults. Appl Physiol Nutr Metab 2016; 41(8): 832-41.
[http://dx.doi.org/10.1139/apnm-2015-0637] [PMID: 27441589]
[22]
Jenkins NT, Landers RQ, Prior SJ, Soni N, Spangenburg EE, Hagberg JM. Effects of acute and chronic endurance exercise on intracellular nitric oxide and superoxide in circulating CD34+ and CD34_ cells. J Appl Physiol (1985) 2011; 111(3): 929-37.
[http://dx.doi.org/10.1152/japplphysiol.00541.2011] [PMID: 21700895]
[23]
Lutz AH, Blumenthal JB, Landers-Ramos RQ, Prior SJ. Exercise-induced endothelial progenitor cell mobilization is attenuated in impaired glucose tolerance and type 2 diabetes. J Appl Physiol 2016; 121(1): 36-41.
[http://dx.doi.org/10.1152/japplphysiol.00349.2016] [PMID: 27197857]
[24]
Prior SJ, Ryan AS. Low clonogenic potential of circulating angiogenic cells is associated with lower density of capillaries in skeletal muscle in patients with impaired glucose tolerance. Diabetes Metab Res Rev 2013; 29(4): 319-25.
[http://dx.doi.org/10.1002/dmrr.2398] [PMID: 23390082]
[25]
Hur J, Yang HM, Yoon CH, et al. Identification of a novel role of T cells in postnatal vasculogenesis: Characterization of endothelial progenitor cell colonies. Circulation 2007; 116(15): 1671-82.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.107.694778] [PMID: 17909106]
[26]
Fadini GP, Losordo D, Dimmeler S. Critical reevaluation of endothelial progenitor cell phenotypes for therapeutic and diagnostic use. Circ Res 2012; 110(4): 624-37.
[http://dx.doi.org/10.1161/CIRCRESAHA.111.243386] [PMID: 22343557]
[27]
Rouhl RPW, Mertens AECS, van Oostenbrugge RJ, et al. Angiogenic T-cells and putative endothelial progenitor cells in hypertension-related cerebral small vessel disease. Stroke 2012; 43(1): 256-8.
[http://dx.doi.org/10.1161/STROKEAHA.111.632208] [PMID: 21980212]
[28]
Weil BR, Kushner EJ, Diehl KJ, Greiner JJ, Stauffer BL, Desouza CA. CD31+ T cells, endothelial function and cardiovascular risk. Heart Lung Circ 2011; 20(10): 659-62.
[http://dx.doi.org/10.1016/j.hlc.2011.06.003] [PMID: 21767986]
[29]
Rehman J, Li J, Orschell CM, March KL. Peripheral blood “endothelial progenitor cells” are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation 2003; 107(8): 1164-9.
[http://dx.doi.org/10.1161/01.CIR.0000058702.69484.A0] [PMID: 12615796]
[30]
Favre J, Terborg N, Horrevoets AJG. The diverse identity of angiogenic monocytes. Eur J Clin Invest 2013; 43(1): 100-7.
[http://dx.doi.org/10.1111/eci.12009] [PMID: 23083351]
[31]
Jaipersad AS, Lip GYH, Silverman S, Shantsila E. The role of monocytes in angiogenesis and atherosclerosis. J Am Coll Cardiol 2014; 63(1): 1-11.
[http://dx.doi.org/10.1016/j.jacc.2013.09.019] [PMID: 24140662]
[32]
Fang M, Zhong L, Jin X, et al. Effect of inflammation on the process of stroke rehabilitation and poststroke depression. Front Psychiatry 2019; 10: 184.
[http://dx.doi.org/10.3389/fpsyt.2019.00184] [PMID: 31031649]
[33]
Chambers SEJ, O’Neill CL, O’Doherty TM, Medina RJ, Stitt AW. The role of immune-related myeloid cells in angiogenesis. Immunobiology 2013; 218(11): 1370-5.
[http://dx.doi.org/10.1016/j.imbio.2013.06.010] [PMID: 23932437]
[34]
Auffray C, Fogg D, Garfa M, et al. Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science (80- ) 2007; 317: 666.
[http://dx.doi.org/10.1126/science.1142883.]
[35]
Ghattas A, Griffiths HR, Devitt A, Lip GYH, Shantsila E. Monocytes in coronary artery disease and atherosclerosis: Where are we now? J Am Coll Cardiol 2013; 62(17): 1541-51.
[http://dx.doi.org/10.1016/j.jacc.2013.07.043] [PMID: 23973684]
[36]
Avraham-Davidi I, Yona S, Grunewald M, et al. On-site education of VEGF-recruited monocytes improves their performance as angiogenic and arteriogenic accessory cells. J Exp Med 2013; 210(12): 2611-25.
[http://dx.doi.org/10.1084/jem.20120690] [PMID: 24166715]
[37]
Marushima A, Nieminen M, Kremenetskaia I, et al. Balanced single-vector co-delivery of VEGF/PDGF-BB improves functional collateralization in chronic cerebral ischemia. J Cereb Blood Flow Metab 2020; 40(2): 404-19.
[http://dx.doi.org/10.1177/0271678X18818298] [PMID: 30621518]
[38]
Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science (80- ) 1997; 275: 964.
[http://dx.doi.org/10.1126/science.275.5302.964]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 18
ISSUE: 1
Year: 2021
Published on: 06 April, 2021
Page: [113 - 122]
Pages: 10
DOI: 10.2174/1567202618666210406125558
Price: $65

Article Metrics

PDF: 275
HTML: 1