Abstract
Low levels of endothelial progenitor cells (EPCs) are associated with cardiovascular (CV) morbidity and mortality. Early indicators of vascular damage represent independent predictors of CV prognosis. The aim of this study was to evaluate the possible association of EPCs and circulating cytokine levels with vascular damage markers in naive hypertensive patients according to sex and to evaluate the role of EPCs in vascular damage progression. We enrolled 60 subjects; circulating EPCs were determined by cytometric analysis, and serum cytokines were determined by chemiluminescence microarray technology. Endothelial function was estimated with the measurement of the reactive hyperemia index (RHI), arterial stiffness (AS) was evaluated with the measurement of carotid-femoral pulse wave velocity (PWV) and carotid intima-media thickness (IMT) was determined by a high-resolution ultrasound B-mode system. Patients were evaluated at baseline and after an average follow-up of 3.0 ± 0.6 years. RHI was correlated with EPCs and inversely related to HOMA, TNF-α, IL-6, hs-CRP, and IL-1β. PWV was positively correlated with HOMA, TNF-α, IL-6, IL-1β, and hs-CRP, and it was inversely related to EPCs. An inverse relationship was observed between c-IMT and EPCs and e-GFR. EPCs were the major predictor of the RHI and PWV. After adjustment for vascular index basal values and the other covariates, EPCs explained 17.0%, 27.7%, and 10.6% of the variability in ΔRHI, ΔPWV, and Δc-IMT at follow-up, respectively. Our study results support the hypothesis of an etiological link between circulating EPCs and morphofunctional vascular parameters in hypertensive subjects. Of interest, circulating EPCs, after adjusting for possible confounding factors, may indicate vascular damage progression.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Hristov M, Zernecke A, Liehn EA, Weber C. Regulation of endothelial progenitor cell homing after arterial injury. Thromb Haemost. 2007;98:274–7.
Schmidt-Lucke C, Rössig L, Fichtlscherer S, Vasa M, Britten M, Kämper U, et al. Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation. 2005;111:2981–7.
Luo S, Xia W, Chen C, Robinson EA, Tao J. Endothelial progenitor cells and hypertension: current concepts and future implications. Clin Sci. 2016;130:2029–42.
Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, et al. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med. 2005;353:999–1007.
Sciacqua A, Scozzafava A, Pujia A, Maio R, Borrello F, Andreozzi F, et al. Interaction between vascular dysfunction and cardiac mass increases the risk of cardiovascular outcomes in essential hypertension. Eur Heart J. 2005;26:921–7.
Liao Y, Chen L, Zeng T, Li Y, Yu F, Hu L, et al. Number of circulating endothelial progenitor cells as a marker of vascular endothelial function for type 2 diabetes. Vasc Med. 2010;15:279–85.
Hill JM, Zalos G, Halcox JPJ, Schenke WH, Waclawiw MA, Quyyumi AA, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003;348:593–600.
Avolio AP, Van Bortel LM, Boutouyrie P, Cockcroft JR, McEniery CM, Protogerou AD, et al. Role of pulse pressure amplification in arterial hypertension: experts’ opinion and review of the data. Hypertension. 2009;54:375–83.
Sciacqua A, Maio R, Miceli S, Pascale A, Carullo G, Grillo N, et al. Association between one-hour post-load plasma glucose levels and vascular stiffness in essential hypertension. PLoS ONE. 2012;7:e44470.
Ceravolo R, Maio R, Pujia A, Sciacqua A, Ventura G, Costa MC, et al. Pulse pressure and endothelial dysfunction in never-treated hypertensive patients. J Am Coll Cardiol. 2003;41:1753–8.
Mattace-Raso F, van der Cammen TJM, Hofman A, van Popele NM, Bos ML, Schalekamp MADH, et al. Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam Study. Circulation. 2006;113:657–63.
Yang Z, Chen L, Su C, Xia W, Wang Y, Wang J, et al. Impaired endothelial progenitor cell activity is associated with reduced arterial elasticity in patients with essential hypertension. Clin Exp Hypertens. 2010;32:444–52.
Mandraffino G, Sardo MA, Riggio S, Loddo S, Imbalzano E, Alibrandi A, et al. Circulating progenitor cells are increased in newly diagnosed untreated hypertensive patients with arterial stiffening but normal carotid intima-media thickness. Hypertens Res. 2011;34:876–83.
Marketou ME, Kalyva A, Parthenakis FI, Pontikoglou C, Maragkoudakis S, Kontaraki JE, et al. Circulating endothelial progenitor cells in hypertensive patients with increased arterial stiffness. J Clin Hypertens. 2014;16:295–300.
Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999;340:115–26.
Perticone F, Maio R, Sciacqua A, Andreozzi F, Iemma G, Perticone M, et al. Endothelial dysfunction and C-reactive protein are risk factors for diabetes in essential hypertension. Diabetes. 2008;57:167–71.
Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB, et al. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care. 2000;23:57–63.
Accattato F, Greco M, Pullano SA, Carè I, Fiorillo AS, Pujia A, et al. Effects of acute physical exercise on oxidative stress and inflammatory status in young, sedentary obese subjects. PLoS ONE. 2017;12:e0178900.
Peters SA, den Ruijter HM, Palmer MK, Grobbee DE, Crouse JR 3rd, O’Leary DH, et al. METEOR Study Investigators. Extensive or restricted ultrasound protocols to measure carotid intima-media thickness: analysis of completeness rates and impact on observed rates of change over time. J Am Soc Echocardiogr. 2012;25:91–100.
Rubinshtein R, Kuvin JT, Soffler M, Lennon RJ, Lavi S, Nelson RE, et al. Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events. Eur Heart J. 2010;31:1142–8.
Mandraffino G, Imbalzano E, Sardo MA, D’Ascola A, Mamone F, Lo Gullo A, et al. Circulating progenitor cells in hypertensive patients with different degrees of cardiovascular involvement. J Hum Hypertens. 2014;28:543–50.
Aragona CO, Imbalzano E, Mamone F, Cairo V, Lo Gullo A, D’Ascola A, et al. Endothelial progenitor cells for diagnosis and prognosis in cardiovascular disease. Stem Cells Int. 2016;2016:8043792.
Fadini GP, de Kreutzenberg SV, Coracina A, Baesso I, Agostini C, Tiengo A, et al. Circulating CD34+ cells, metabolic syndrome, and cardiovascular risk. Eur Heart J. 2006;27:2247–55.
Andreozzi F, Laratta E, Sciacqua A, Perticone F, Sesti G. Angiotensin II impairs the insulin signaling pathway promoting production of nitric oxide by inducing phosphorylation of insulin receptor substrate-1 on Ser312 and Ser616 in human umbilical vein endothelial cells. Circ Res. 2004;94:1211–8.
Aicher A, Heeschen C, Dimmeler S. The role of NOS3 in stem cell mobilization. Trends Mol Med. 2004;10:421–5.
Cubbon RM, Kahn MB, Wheatcroft SB. Effects of insulin resistance on endothelial progenitor cells and vascular repair. Clin Sci. 2009;117:173–90.
Mahmud A, Feely J. Arterial stiffness is related to systemic inflammation in essential hypertension. Hypertension. 2005;46:1118–22.
Tomiyama H, Yamashina A. Non-invasive vascular function tests: their pathophysiological background and clinical application. Circ J. 2010;74:24–33.
Mahmud A, Feely J. Arterial stiffness and the renin-angiotensin-aldosterone system. J Renin Angiotensin Aldosterone Syst. 2004;5:102–8.
Lee PS, Poh KK. Endothelial progenitor cells in cardiovascular diseases. World J Stem Cells. 2014;6:355–66.
Raptis AE, Markakis KP, Mazioti MC, Ikonomidis I, Maratou EP, Vlahakos DV, et al. Effect of aliskiren on circulating endothelial progenitor cells and vascular function in patients with type 2 diabetes and essential hypertension. Am J Hypertens. 2015;28:22–9.
Cacciatore F, Bruzzese G, Vitale DF, Liguori A, de Nigris F, Fiorito C, et al. Effects of ACE inhibition on circulating endothelial progenitor cells, vascular damage, and oxidative stress in hypertensive patients. Eur J Clin Pharm. 2011;67:877–83.
Suzuki R, Fukuda N, Katakawa M, Tsunemi A, Tahira Y, Matsumoto T, et al. Effects of an angiotensin II receptor blocker on the impaired function of endothelial progenitor cells in patients with essential hypertension. Am J Hypertens. 2014;27:695–701.
Chen L, Ding ML, Wu F, He W, Li J, Zhang XY, et al. Impaired endothelial repair capacity of early endothelial progenitor cells in hypertensive patients with primary hyperaldosteronemia: role of 5,6,7,8-tetrahydrobiopterin oxidation and endothelial nitric oxide synthase uncoupling. Hypertension. 2016;67:430–9.
Sugiura T, Kondo T, Kureishi-Bando Y, Numaguchi Y, Yoshida O, Dohi Y, et al. Nifedipine improves endothelial function: role of endothelial progenitor cells. Hypertension. 2008;52:491–8.
Yao EH, Fukuda N, Matsumoto T, Katakawa M, Yamamoto C, Han Y, et al. Effects of the antioxidative beta-blocker celiprolol on endothelial progenitor cells in hypertensive rats. Am J Hypertens. 2008;21:1062–8.
Pastori D, Farcomeni A, Milanese A, Del Sole F, Menichelli D, Hiatt WR, et al. Statins and major adverse limb events in patients with peripheral artery disease: a systematic review and meta-analysis. Thromb Haemost. 2020;120:866–75.
Golab-Janowska M, Paczkowska E, Machalinski B, Meller A, Kotlega D, Safranow K, et al. Statins therapy is associated with increased populations of early endothelial progenitor (CD133+/VEGFR2+) and endothelial (CD34-/CD133-/VEGFR2+) cells in patients with acute ischemic stroke. Curr Neurovasc Res. 2018;15:120–8.
Park A, Barrera-Ramirez J, Ranasinghe I, Pilon S, Sy R, Fergusson D, et al. Use of statins to augment progenitor cell function in preclinical and clinical studies of regenerative therapy: a systematic review. Stem Cell Rev Rep. 2016;12:327–39.
Briguori C, Quintavalle C, D’Alessio F, Donahue M, Roscigno G, De Micco F, et al. Impact of statin therapy intensity on endothelial progenitor cells after percutaneous coronary intervention in diabetic patients. The REMEDY-EPC late study. Int J Cardiol. 2017;244:112–8.
Chantzichristos VG, Agouridis AP, Moutzouri E, Stellos K, Elisaf MS, et al. Effect of rosuvastatin or its combination with omega-3 fatty acids on circulating CD34(+) progenitor cells and on endothelial colony formation in patients with mixed dyslipidaemia. Atherosclerosis. 2016;251:240–7.
Author information
Authors and Affiliations
Contributions
All authors contributed to data collection and analysis, drafting of the article, and interpretation of the results. All authors provided critical feedback, assisted in the revision of the article, and approved the final version.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no competing interests.
Ethical approval
The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the local ethics committee (Comitato Etico Azienda Ospedaliera “Mater Domini”) (cod. protocol number 2021.63).
Informed consent
Informed consent was obtained from all subjects involved in the study.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
About this article
Cite this article
Cassano, V., Tripepi, G., Perticone, M. et al. Endothelial progenitor cells predict vascular damage progression in naive hypertensive patients according to sex. Hypertens Res 44, 1451–1461 (2021). https://doi.org/10.1038/s41440-021-00716-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41440-021-00716-z
Keywords
This article is cited by
-
Mean platelet volume (MPV) as new marker of diabetic macrovascular complications in patients with different glucose homeostasis
Cardiovascular Diabetology (2024)
-
Association between non-dipping blood pressure pattern and different glucometabolic profile during oral glucose tolerance test
Internal and Emergency Medicine (2024)
-
Circulating endothelial and angiogenic cells predict hippocampal volume as a function of HIV status
Journal of NeuroVirology (2023)