nach oben

Erschienen in:

24.01.2023 | IM - ORIGINAL

Vascular health in subjects with rheumatoid arthritis: assessment of endothelial function indices and serum biomarkers of vascular damage

verfasst von: Mario Daidone, Alessandro Del Cuore, Alessandra Casuccio, Tiziana Di Chiara, Giuliana Guggino, Domenico Di Raimondo, Maria Grazia Puleo, Angelo Ferrante, Rosario Scaglione, Antonio Pinto, Antonino Tuttolomondo

Erschienen in: Internal and Emergency Medicine | Ausgabe 2/2023

Einloggen, um Zugang zu erhalten

Abstract

Background

The cardiovascular risk (CVD) in patients with rheumatoid arthritis (RA) is 1.5–2 times higher than that in individuals of the same age and sex.

Aims

To analyse the degree of endothelial dysfunction, the atherogenic immunoinflammatory serum background and the relationships among some vascular indices, cardiovascular comorbidities, and cognitive performance in subjects with RA.

Patients and methods

All consecutive patients with a rheumatoid arthritis diagnosis admitted to the Rheumatology Ward of “Policlinico Paolo Giaccone” Hospital of Palermo were enrolled from July 2019 to September 2020. We evaluated our patients’ cognitive functions by administering the Mini-Mental State Examination (MMSE). Reactive Hyperaemia Index (RHI) was evaluated for assessment of endothelial function. Serum levels of angiopoietin 2, osteopontin and pentraxin 3 were assessed by blood collection.

Results

Fifty-eight consecutive patients with RA and 40 control subjects were analysed. RA patients showed significantly lower mean RHI values, significantly higher mean Augmentation Index (AIX) values and significantly lower mean Mini-Mental State Examination (MMSE) score values than the control group. Patients with rheumatoid arthritis also showed higher mean serum values of pentraxin 3 and angiopoietin 2 than healthy controls. Multivariate logistic regression analysis showed a significant association between pentraxin 3 and angiopoietin 2 and the presence of RA.

Discussion

Angiopoietin 2 and pentraxin 3 could be considered surrogate biomarkers of endothelial activation and vascular disease, as they could play an essential role in the regulation of endothelial integrity and inflammation.

Micha R, Imamura F, Wyler von Ballmoos M, Solomon DH, Hernan MA, Ridker PM et al (2011) Systematic review and meta-analysis of methotrexate use and risk of cardiovascular disease. Am J Cardiol 108(9):1362–1370CrossRefPubMedPubMedCentral

Stevens RJ, Douglas KMJ, Saratzis AN, Kitas GD (2005) Inflammation and atherosclerosis in rheumatoid arthritis. Expert Rev Mol Med 7:1–24. https://doi.org/10.1017/S1462399405009154CrossRefPubMed

Choy E (2012) Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatol Oxf Engl 51(Suppl 5):v3-11. https://doi.org/10.1093/rheumatology/kes113CrossRef

Karpouzas GA, Malpeso J, Choi T-Y, Li D, Munoz S, Budoff MJ (2014) Prevalence, extent and composition of coronary plaque in patients with rheumatoid arthritis without symptoms or prior diagnosis of coronary artery disease. Ann Rheum Dis 73:1797–1804. https://doi.org/10.1136/annrheumdis-2013-203617CrossRefPubMed

Liang KP, Maradit-Kremers H, Crowson CS, Snyder MR, Therneau TM, Roger VL, Gabriel SE (2009) Autoantibodies and the risk of cardiovascular events. J Rheumatol 36:2462–2469. https://doi.org/10.3899/jrheum.090188CrossRefPubMedPubMedCentral

Hjeltnes G, Hollan I, Førre Ø, Wiik A, Mikkelsen K, Agewall S (2011) Anti-CCP and RF IgM: predictors of impaired endothelial function in rheumatoid arthritis patients. Scand J Rheumatol 40:422–427. https://doi.org/10.3109/03009742.2011.585350CrossRefPubMed

Spasovski D, Latifi A, Osmani B et al (2013) Determination of the diagnostic values of asymmetric dimethylarginine as an indicator for evaluation of the endothelial dysfunction in patients with rheumatoid arthritis. Arthritis 818037:10

Favero G, Paganelli C, Buffoli B, Rodella LF, Rezzani R (2014) Endothelium and its alterations in cardiovascular diseases: life style intervention. BioMedResearch Int 801896:28

Khan BV, Harrison DG, Olbrych MT, Alexander RW, Medford RM (1996) Nitric oxide regulates vascular cell adhesion molecule 1 gene expression and redox-sensitive transcriptional events in human vascular endothelial cells. Proceed Nat Acad Sci USA 93(17):9114–9119CrossRef

10.

Stocker R, Keaney JF Jr (2004) Role of oxidative modifications in atherosclerosis. Physiol Rev 84(4):1381–1478CrossRefPubMed

11.

Versari D, Daghini E, Virdis A, Ghiadoni L, Taddei S (2009) Endothelial dysfunction as a target for prevention of cardiovascular disease. Diabetes Care 32(Suppl 2):S314-321. https://doi.org/10.2337/dc09-S330CrossRefPubMedPubMedCentral

12.

MacDonald IJ, Liu SC, Su CM, et al. (2018) Implications of angiogenesis involvement in arthritis. Int J Mol Sci 19(7):2012

13.

Su L, Zhai R, Sheu CC et al (2009) Genetic variants in the angiopoietin-2 gene are associated with increased risk of ARDS. Intensive Care Med 35:1024–1030CrossRefPubMedPubMedCentral

14.

Wang LH, Tsai HC, Cheng YC et al (2017) CTGF promotes osteosarcoma angiogenesis by regulating MiR-543/angiopoietin 2 signaling. Cancer Lett 391:28–37CrossRefPubMed

15.

Fagiani E, Christofori G (2013) Angiopoietins in angiogenesis. Cancer Lett 328:18–26CrossRefPubMed

16.

Ortega-Hernandez OD, Bassi N, Shoenfeld Y et al (2009) The long pentraxin 3 and its role in autoimmunity. Semin Arthritis Rheum 39:3854CrossRef

17.

Xu G, Nie H, Li N, Zheng W, Zhang D, Feng G, Ni L, Xu R, Hong J, Zhang JZ (2005) Role of osteopontin in amplification and perpetuation of rheumatoid synovitis. J Clin Invest 115:1060–1067CrossRefPubMedPubMedCentral

18.

Pilling D, Cox N, Vakil V et al (2015) The long pentraxin PTX3 promotes fibrocyte differentiation. PLoS ONE 10:E0119709CrossRefPubMedPubMedCentral

19.

Kay J, Upchurch KS (2012) ACR/EULAR 2010 rheumatoid arthritis classification criteria. Rheumatol Oxf Engl. https://doi.org/10.1093/rheumatology/kes279CrossRef

20.

Prevoo MLV, Hof MA, Kuper HHV, Leeuwen MAV, de Putte LB, Van Riel PL (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. https://doi.org/10.1002/art.1780380107CrossRefPubMed

21.

Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. J Psychiatric Res 12(3):189–198

22.

Versari D, Daghini E, Virdis A, Ghiadoni L, Taddei S (2009) Endothelial dysfunction as a target for prevention of cardio- vascular disease. Diabetes Care 32(Supplement 2):S314–S321CrossRefPubMedPubMedCentral

23.

Lotz M (1995) Interleukin-6: a comprehensive review. Cancer Treat- Ment Res 80:209–233CrossRef

24.

Schmedtje JF Jr, Ji Y-S, Liu W-L, DuBois RN, Runge MS (1997) Hypoxia induces cyclooxygenase-2 via the NF-κB P65 transcription factor in human vascular endothelial cells. J BiologicalChem 272(1):601–608

25.

Prior P, Symmons DPM, Scott DL, Brown R, Hawkins CF (1984) Cause of death in rheumatoid arthritis. Rheumatology 23:92–99. https://doi.org/10.1093/rheumatology/23.2.92CrossRef

26.

Panoulas VF, Douglas KMJ, Milionis HJ, Stavropoulos-Kalinglou A, Nightingale P, Kita MD, Tselios AL, Metsios GS, Elisaf MS, Kitas GD (2007) Prevalence and associations of hypertension and its control in patients with rheumatoid arthritis. Rheumatol Oxf Engl 46:1477–1482. https://doi.org/10.1093/rheumatology/kem169CrossRef

27.

Pincus T, Callahan LF (1986) Taking mortality in rheumatoid arthritis seriously-predictive markers. Socioecon Status Comorb J Rheumatol 13:841–845

28.

Garlanda C, Bottazzi B, Bastone A, Mantovani A (2005) Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition and female fertility. Annu Rev Immunol 23:337–366CrossRefPubMed

29.

Cieslik P, Hrycek A (2012) Long Pentraxin 3 (PTX3) in the light of its structure, mechanism of action and clinical implications. Autoimmunity 45:119128CrossRef

30.

Garlanda C, Bottazzi B, Moalli F, Deban L, Molla F, Latini R et al (2011) Pentraxins and atherosclerosis: the role of PTX3. Curr Pharm Des 17:38–46CrossRefPubMed

31.

Bosutti A, Grassi G, Zanetti M, Aleksova A, Zecchin M, Sinagra G, Biolo G, Guarnieri G (2007) Relation between the plasma levels of LDL-cholesterol and the expression of the early marker of inflammation long pentraxin PTX3 and the stress response gene P66ShcA in pacemaker-implanted patients. Clin Exp Med 7:16–23CrossRefPubMed

32.

Hollan I, Bottazzi B, Cuccovillo I et al (2010) Increased levels of serum pentraxin 3, a novel cardiovascular biomarker, in patients with inflammatory rheumatic disease. Arthritis Care Res (Hoboken) 62:378385CrossRef

33.

Wang H, Wang K, Wang C et al (2013) Increased plasma levels of pentraxin 3 in patients with multiple sclerosis and neuromyelitis optica. Mult Scler 19:926931CrossRef

34.

Luchetti MM, Piccinini G, Mantovani A, Peri G, Matteucci C, Pomponio G, Fratini M, Fraticelli P, Sambo P, Di Loreto C, Doni A, Introna M, Gabrielli A (2000) Expression and production of the long pentraxin PTX3 in rheumatoid arthritis (RA). Clin Exp Immunol 119:196–202CrossRefPubMedPubMedCentral

35.

Barksby HE, Hui W, Wappler I, Peters HH, Milner JM, Richards CD et al (2006) Interleukin-1 in combination with oncostatin M up-regulates multiple genes in chondrocytes: implications for cartilage destruction and repair. Arthritis Rheum 54(2):540–545CrossRefPubMed

36.

Cawston TE, Curry VA, Summers CA, Clark IM, Riley GP, LifePF, et al (1998) The role of Oncostatin M in animal and human connective tissue collagen turnover and its localization within the rheumatoid joint. Arthritis Rheum 41(10):1760–1771CrossRefPubMed

37.

Hui W, Cawston TE, Richards CD, Rowan AD (2005) A model for inflammatory arthritis highlights a role for Oncostatin M in proinflammatory cytokine-induced bone destruction via RANK/RANKL. Arthritis Res Ther 7(1):R57-64CrossRefPubMed

38.

Rowan AD, Hui W, Cawston TE, Richards CD (2003) Adenoviral gene transfer of interleukin-1 in combination with Oncostatin M induces significant joint damage in a murine model. Am J Pathol 162(6):1975–1984CrossRefPubMedPubMedCentral

39.

Takahara K, Iioka T, Furukawa K, Uchida T, Nakashima M, Tsukazaki T, Shindo H (2004) Autocrine/paracrine role of the angiopoietin-1 and -2/Tie2 system in cell proliferation and chemotaxis of cultured fibroblastic synoviocytes in rheumatoid arthritis. Hum Pathol 35:150–158. https://doi.org/10.1016/j.humpath.2003.11.010CrossRefPubMed

40.

Chen X, Fu W, Tung CE, Ward NL (2009) Angiopoietin-1 induces neurite outgrowth of PC12 cells in a tie2-independent, beta1-integrin-dependent manner. Neurosci Res 64:348–354CrossRefPubMedPubMedCentral

41.

Scholz A et al (2011) Angiopoietin-2 promotes myeloid cell infiltration in a beta(2)- integrin-dependent manner. Blood 118:5050–5059CrossRefPubMed

42.

Lee J et al (2013) Angiopoietin-1 guides directional angiogenesis through integrin Avb5 signaling for recovery of ischemic retinopathy. Sci Transl Med 5:203127CrossRef

43.

Felcht M et al (2012) Angiopoietin-2 differentially regulates angiogenesis through TIE2 and integrin signaling. J Clin Invest 122:1991–2005CrossRefPubMedPubMedCentral

44.

Roviezzo F, Tsigkos S, Kotanidou A, Bucci M, Brancaleone V, Cirino G, Papapetropoulos A (2005) Angiopoietin-2 causes inflammation in vivo by promoting vascular leakage. J Pharmacol Exp Ther 314:738–744. https://doi.org/10.1124/jpet.105.086553CrossRefPubMed

45.

Lemieux C, Maliba R, Favier J, Théorêt J-F, Merhi Y, Sirois MG (2005) Angiopoietins can directly activate endothelial cells and neutrophils to promote proinflammatory responses. Blood 105:1523–1530. https://doi.org/10.1182/blood-2004-09-3531CrossRefPubMed

46.

Lopez-Mejias R, Corrales A, Genre F et al (2013) Angiopoietin-2 serum levels correlate with severity, early onset and cardiovascular disease in patients with rheumatoid arthritis. ClinExpRheumatol 31:761–766

47.

Patarca R, Saavedra RA, Cantor H (1993) Molecular and cellular basis of genetic resistance to bacterial infection: the role of the early T lymphocyte activation-1/osteopontin gene. Crit Rev Immunol 13:225–246PubMed

48.

Sodek J, Ganss B, McKee MD (2000) Osteopontin. Crit Rev Oral Biol Med 11:279–303CrossRefPubMed

49.

Denhardt DT, Noda M, O’Regan AW, Pavlin D, Berman JS (2001) Osteopontin as a means to cope with environmental insults: regulation of inflammation, tissue remodeling, and cell survival. J Clin Invest 107:1055–1061CrossRefPubMedPubMedCentral

50.

Ji HI, Lee SH, Song R et al (2014) Serum level of osteopontin as an inflammatory marker does not indicate disease activity or responsiveness to therapeutic treatments in patients with rheumatoid arthritis. Clin Rheumatol 33:397–402CrossRefPubMed

51.

Laurent S et al (2006) Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 27:2588–2605CrossRefPubMed

52.

Ohmori R et al (2003) Plasma osteopontin levels are associated with the presence and extent of coronary artery disease. Atherosclerosis 170:333–337CrossRefPubMed

53.

Kato R et al (2006) High plasma levels of osteopontin in patients with restenosis after percutaneous coronary intervention. Arterioscler Thromb Vasc Biol 26:E1-2CrossRefPubMed

Titel: Vascular health in subjects with rheumatoid arthritis: assessment of endothelial function indices and serum biomarkers of vascular damage
verfasst von: Mario Daidone
Alessandro Del Cuore
Alessandra Casuccio
Tiziana Di Chiara
Giuliana Guggino
Domenico Di Raimondo
Maria Grazia Puleo
Angelo Ferrante
Rosario Scaglione
Antonio Pinto
Antonino Tuttolomondo
Publikationsdatum: 24.01.2023
Verlag: Springer International Publishing
Erschienen in: Internal and Emergency Medicine / Ausgabe 2/2023
Print ISSN: 1828-0447
Elektronische ISSN: 1970-9366
DOI: https://doi.org/10.1007/s11739-023-03192-0

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Vascular health in subjects with rheumatoid arthritis: assessment of endothelial function indices and serum biomarkers of vascular damage