PDF herunterladen
Int J Angiol 2017; 26(01): 036-042
DOI: 10.1055/s-0036-1593445
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Endothelial Progenitor Cells as a Marker of Endothelial Dysfunction and Atherosclerosis in Ankylosing Spondylitis: A Cross-Sectional Study

Inderjeet Verma
1   Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India
,
Ashit Syngle
2   Cardio Rheuma and Healing Touch City Clinic, Chandigarh and Consultant Rheumatologist Fortis Multi Specialty Hospital, Mohali, Chandigarh, India
,
Pawan Krishan
1   Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India
,
Nidhi Garg
1   Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
03. Oktober 2016 (online)

    Lizenzen und Reprints

Abstract

Endothelial progenitor cells (EPCs) have reparative potential in overcoming the endothelial dysfunction and reducing cardiovascular risk. EPC depletion has been demonstrated in the setting of established atherosclerotic diseases. We evaluated whether reduced EPCs population are associated with endothelial dysfunction, subclinical atherosclerosis, and inflammatory markers in ankylosing spondylitis (AS) patients without any known traditional cardiovascular risk factor. We performed a cross-sectional study of 30 consecutive AS patients and 25 age- and sex-matched healthy controls. Patients with traditional cardiovascular risk factors were excluded. Circulating EPCs (CD34+/CD133+) were quantified by flow cytometry. The assessment of endothelial function by brachial artery flow-mediated dilatation (FMD) and ultrasound assessment of carotid intima-media thickness (CIMT) was measured in both the groups. EPCs cells were significantly (0.020 ± 0.001 vs. 0.040 ± 0.010%, p < 0.001) reduced in patients with AS compared with healthy controls. Endothelial function (7.35 ± 2.54 vs. 10.27 ± 1.73, p = 0.002), CIMT (0.63 ± 0.01 vs. 0.35 ± 0.02, p < 0.001), and inflammatory markers were also significantly (p < 0.01) altered as compared with controls. EPCs inversely correlated with tumor necrosis factor (TNF)-α and C-reactive protein (CRP) and positively correlated with endothelial function. Present study results demonstrate depleted EPC population in AS patients compared with controls. Increased level of CRP and TNF-α appears to play a key role in EPC depletion and the latter contributes to endothelial dysfunction and atherosclerosis in AS. EPC population would, therefore, represent an attractive measure of endothelial dysfunction and accelerated atherosclerosis disease associated with AS.

Keywords

ankylosing spondylitis - endothelial progenitor cells - endothelial function - carotid intima-media thickness - inflammation

Disclosure

None.


 

  • References

  • 1 Azevedo VF, Pecoits-Filho R. Atherosclerosis and endothelial dysfunction in patients with ankylosing spondylitis. Rheumatol Int 2010; 30 (11) 1411-1416
    CrossrefPubMedGoogle Scholar
  • 2 Landmesser U, Hornig B, Drexler H. Endothelial function: a critical determinant in atherosclerosis?. Circulation 2004; 109 (21) (Suppl. 01) II27-II33
    CrossrefPubMedGoogle Scholar
  • 3 Willerson JT, Ridker PM. Inflammation as a cardiovascular risk factor. Circulation 2004; 109 (21) (Suppl. 01) II2-II10
    CrossrefPubMedGoogle Scholar
  • 4 Goodson NJ, Symmons DP, Scott DG, Bunn D, Lunt M, Silman AJ. Baseline levels of C-reactive protein and prediction of death from cardiovascular disease in patients with inflammatory polyarthritis: a ten-year followup study of a primary care-based inception cohort. Arthritis Rheum 2005; 52 (8) 2293-2299
    CrossrefPubMedGoogle Scholar
  • 5 Mathieu S, Joly H, Baron G , et al. Trend towards increased arterial stiffness or intima-media thickness in ankylosing spondylitis patients without clinically evident cardiovascular disease. Rheumatology (Oxford) 2008; 47 (8) 1203-1207
    CrossrefPubMedGoogle Scholar
  • 6 Asahara T, Murohara T, Sullivan A , et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275 (5302): 964-967
    CrossrefPubMedGoogle Scholar
  • 7 Gill M, Dias S, Hattori K , et al. Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells. Circ Res 2001; 88 (2) 167-174
    CrossrefPubMedGoogle Scholar
  • 8 del Rincón ID, Williams K, Stern MP, Freeman GL, Escalante A. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum 2001; 44 (12) 2737-2745
    CrossrefPubMedGoogle Scholar
  • 9 Asanuma Y, Oeser A, Shintani AK , et al. Premature coronary-artery atherosclerosis in systemic lupus erythematosus. N Engl J Med 2003; 349 (25) 2407-2415
    CrossrefPubMedGoogle Scholar
  • 10 van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984; 27 (4) 361-368
    CrossrefPubMedGoogle Scholar
  • 11 Garg N, Krishan P, Syngle A. Rosuvastatin improves endothelial dysfunction in ankylosing spondylitis. Clin Rheumatol 2015; 34 (6) 1065-1071
    CrossrefPubMedGoogle Scholar
  • 12 Huang K, Zou CC, Yang XZ, Chen XQ, Liang L. Carotid intima-media thickness and serum endothelial marker levels in obese children with metabolic syndrome. Arch Pediatr Adolesc Med 2010; 164 (9) 846-851
    CrossrefPubMedGoogle Scholar
  • 13 Allanore Y, Batteux F, Avouac J, Assous N, Weill B, Kahan A. Levels of circulating endothelial progenitor cells in systemic sclerosis. Clin Exp Rheumatol 2007; 25 (1) 60-66
    PubMedGoogle Scholar
  • 14 Herbrig K, Haensel S, Oelschlaegel U, Pistrosch F, Foerster S, Passauer J. Endothelial dysfunction in patients with rheumatoid arthritis is associated with a reduced number and impaired function of endothelial progenitor cells. Ann Rheum Dis 2006; 65 (2) 157-163
    CrossrefPubMedGoogle Scholar
  • 15 Choe JY, Lee MY, Rheem I, Rhee MY, Park SH, Kim SK. No differences of carotid intima-media thickness between young patients with ankylosing spondylitis and healthy controls. Joint Bone Spine 2008; 75 (5) 548-553
    CrossrefPubMedGoogle Scholar
  • 16 Shoenfeld Y, Gerli R, Doria A , et al. Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation 2005; 112 (21) 3337-3347
    CrossrefPubMedGoogle Scholar
  • 17 Haque S, Alexander MY, Bruce IN. Endothelial progenitor cells: a new player in lupus?. Arthritis Res Ther 2012; 14 (1) 203-213
    CrossrefPubMedGoogle Scholar
  • 18 Hill JM, Zalos G, Halcox JP , et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 2003; 348 (7) 593-600
    CrossrefPubMedGoogle Scholar
  • 19 Verma I, Syngle A, Krishan P. Endothelial progenitor cell biology in ankylosing spondylitis. Int J Rheum Dis 2015; 18 (3) 336-340
    CrossrefPubMedGoogle Scholar
  • 20 Sastry KV, Moudgal RP, Mohan J, Tyagi JS, Rao GS. Spectrophotometric determination of serum nitrite and nitrate by copper-cadmium alloy. Anal Biochem 2002; 306 (1) 79-82
    CrossrefPubMedGoogle Scholar
  • 21 van Ejick IC, Peters MJL, Seme EH , et al. Microvascular function is impaired in ankylosing spondylitis and improves after tumor necrosis factor αblockade. Ann Rheum Dis 2009; 68 (3) 362-366
    CrossrefPubMedGoogle Scholar
  • 22 Verma S, Kuliszewski MA, Li SH , et al. C-reactive protein attenuates endothelial progenitor cell survival, differentiation, and function: further evidence of a mechanistic link between C-reactive protein and cardiovascular disease. Circulation 2004; 109 (17) 2058-2067
    CrossrefPubMedGoogle Scholar
  • 23 Grisar J, Aletaha D, Steiner CW , et al. Endothelial progenitor cells in active rheumatoid arthritis: effects of tumour necrosis factor and glucocorticoid therapy. Ann Rheum Dis 2007; 66 (10) 1284-1288
    CrossrefPubMedGoogle Scholar
  • 24 Westerweel PE, Luijten RK, Hoefer IE, Koomans HA, Derksen RH, Verhaar MC. Haematopoietic and endothelial progenitor cells are deficient in quiescent systemic lupus erythematosus. Ann Rheum Dis 2007; 66 (7) 865-870
    CrossrefPubMedGoogle Scholar
  • 25 Park YJ, Kim JY, Park J, Choi JJ, Kim WU, Cho CS. Bone erosion is associated with reduction of circulating endothelial progenitor cells and endothelial dysfunction in rheumatoid arthritis. Arthritis Rheumatol 2014; 66 (6) 1450-1460
    CrossrefPubMedGoogle Scholar
  • 26 Werner N, Wassmann S, Ahlers P , et al. Endothelial progenitor cells correlate with endothelial function in patients with coronary artery disease. Basic Res Cardiol 2007; 102 (6) 565-571
    CrossrefPubMedGoogle Scholar
  • 27 Imanishi T, Moriwaki C, Hano T, Nishio I. Endothelial progenitor cell senescence is accelerated in both experimental hypertensive rats and patients with essential hypertension. J Hypertens 2005; 23 (10) 1831-1837
    CrossrefPubMedGoogle Scholar
  • 28 Sibal L, Aldibbiat A, Agarwal SC , et al. Circulating endothelial progenitor cells, endothelial function, carotid intima-media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria. Diabetologia 2009; 52 (8) 1464-1473
    CrossrefPubMedGoogle Scholar
  • 29 Mudau M, Genis A, Lochner A, Strijdom H. Endothelial dysfunction: the early predictor of atherosclerosis. Cardiovasc J Afr 2012; 23 (4) 222-231
    CrossrefPubMedGoogle Scholar
  • 30 Wofford JL, Kahl FR, Howard GR, McKinney WM, Toole JF, Crouse III JR. Relation of extent of extracranial carotid artery atherosclerosis as measured by B-mode ultrasound to the extent of coronary atherosclerosis. Arterioscler Thromb 1991; 11 (6) 1786-1794
    CrossrefPubMedGoogle Scholar
  • 31 Lekakis JP, Papamichael CM, Cimponeriu AT , et al. Atherosclerotic changes of extracoronary arteries are associated with the extent of coronary atherosclerosis. Am J Cardiol 2000; 85 (8) 949-952
    CrossrefPubMedGoogle Scholar
  • 32 Sharma SK, Prasad KT, Handa R, Sharma SK. Increased prevalence of subclinical atherosclerosis in ankylosing spondylitis. Indian J Rheumatol 2015; 10 (2) 53-57
    CrossrefPubMedGoogle Scholar
  • 33 Fadini GP, Coracina A, Baesso I , et al. Peripheral blood CD34+KDR+ endothelial progenitor cells are determinants of subclinical atherosclerosis in a middle-aged general population. Stroke 2006; 37 (9) 2277-2282
    CrossrefPubMedGoogle Scholar
  • 34 Ridker PM. Inflammatory biomarkers and risks of myocardial infarction, stroke, diabetes, and total mortality: implications for longevity. Nutr Rev 2007; 65 (12 Pt 2): S253-S259
    CrossrefPubMedGoogle Scholar
  • 35 Grisar J, Aletaha D, Steiner CW , et al. Depletion of endothelial progenitor cells in the peripheral blood of patients with rheumatoid arthritis. Circulation 2005; 111 (2) 204-211
    CrossrefPubMedGoogle Scholar
  • 36 Moonen JR, de Leeuw K, van Seijen XJ , et al. Reduced number and impaired function of circulating progenitor cells in patients with systemic lupus erythematosus. Arthritis Res Ther 2007; 9 (4) R84
    CrossrefPubMedGoogle Scholar
  • 37 Wang HY, Gao PJ, Ji KD , et al. Circulating endothelial progenitor cells, C-reactive protein and severity of coronary stenosis in Chinese patients with coronary artery disease. Hypertens Res 2007; 30 (2) 133-141
    CrossrefPubMedGoogle Scholar
  • 38 Suh W, Kim KL, Choi JH , et al. C-reactive protein impairs angiogenic functions and decreases the secretion of arteriogenic chemo-cytokines in human endothelial progenitor cells. Biochem Biophys Res Commun 2004; 321 (1) 65-71
    CrossrefPubMedGoogle Scholar
  • 39 Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000; 102 (18) 2165-2168
    CrossrefPubMedGoogle Scholar
  • 40 de Groot K, Goldberg C, Bahlmann FH , et al. Vascular endothelial damage and repair in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 2007; 56 (11) 3847-3853
    CrossrefPubMedGoogle Scholar