E Ammirati1, E P Bozzolo2, R Contri3, A Baragetti4, A G Palini5, D Cianflone6, M Banfi7, P Uboldi8, G Bottoni9, I Scotti10, A Pirillo11, L Grigore12, K Garlaschelli13, C Monaco14, A L Catapano15, M G Sabbadini16, A A Manfredi17, G D Norata18. 1. San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy; The Heart Transplantation Division, Ospedale Niguarda Ca' Granda, Milan, Italy. Electronic address: ammirati.enrico@hsr.it. 2. The Department of Medicine, San Raffaele Scientific Institute, Milan, Italy. Electronic address: bozzolo.enrica@hsr.it. 3. San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy. Electronic address: rachele.contri@gmail.com. 4. Center for The Study of Atherosclerosis, Italian Society for The Study of Atherosclerosis Lombardia Chapter, Bassini Hospital Cinisello Balsamo, Milan, Italy; Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy. Electronic address: andrea.baragetti@unimi.it. 5. San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy; The Flow Cytometry Resource, Advanced Cytometry Technical Applications Laboratory, Milan, Italy; Nestlé Institute of Health Science, Flow Cytometry, EPFL Innovation Park, 1015 Lausanne, Switzerland. Electronic address: palini.alessio@hsr.it. 6. San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy. Electronic address: cianflone.domenico@hsr.it. 7. San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy. Electronic address: banfi.michela@hsr.it. 8. Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy. Electronic address: Patrizia.Uboldi@unimi.it. 9. The Hull York Medical School, York, UK. Electronic address: grace.bottoni@gmail.com. 10. San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy. Electronic address: Scotti.isabella@hsr.it. 11. Center for The Study of Atherosclerosis, Italian Society for The Study of Atherosclerosis Lombardia Chapter, Bassini Hospital Cinisello Balsamo, Milan, Italy. Electronic address: Angela.Pirillo@guest.unimi.it. 12. Center for The Study of Atherosclerosis, Italian Society for The Study of Atherosclerosis Lombardia Chapter, Bassini Hospital Cinisello Balsamo, Milan, Italy; The Multimedica IRCCS, Milan, Italy. Electronic address: Grigore.centroatero@gmail.com. 13. Center for The Study of Atherosclerosis, Italian Society for The Study of Atherosclerosis Lombardia Chapter, Bassini Hospital Cinisello Balsamo, Milan, Italy. Electronic address: Garlaschelli.centroatero@gmail.com. 14. The University of Oxford, UK. Electronic address: claudia.monaco@kennedy.ox.ac.uk. 15. Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy; The Multimedica IRCCS, Milan, Italy. Electronic address: Alberico.Catapano@unimi.it. 16. The Department of Medicine, San Raffaele Scientific Institute, Milan, Italy. Electronic address: sabbadini.mariagrazia@hsr.it. 17. The Department of Medicine, San Raffaele Scientific Institute, Milan, Italy. Electronic address: manfredi.angelo@hsr.it. 18. Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy; The Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University, London, UK. Electronic address: Danilo.Norata@unimi.it.
Abstract
BACKGROUND AND AIM: Patients with systemic lupus erythematosus (SLE) have a higher prevalence of subclinical atherosclerosis and higher risk of cardiovascular (CV) events compared to the general population. The relative contribution of CV-, immune- and disease-related risk factors to accelerated atherogenesis in SLE is unclear. METHODS AND RESULTS: Fifty SLE patients with long-lasting disease (mean age 44 ± 10 years, 86% female) and 50 sex- and age-matched control subjects were studied. Common carotid artery intima-media thickness (CCA-IMT) was used as a surrogate marker of atherosclerosis. We evaluated traditional and immune- and disease-related factors, assessed multiple T-cell subsets by 10-parameter-eight-colour polychromatic flow cytometry and addressed the effect of pharmacological therapies on CCA-IMT. In SLE patients, among several cardiometabolic risk factors, only high-density lipoprotein levels (HDL) and their adenosine triphosphate-binding cassette transporter 1 (ABCA-1)-dependent cholesterol efflux capacity were markedly reduced (p < 0.01), whereas the CCA-IMT was significantly increased (p = 0.03) compared to controls. CCA-IMT correlated with systolic blood pressure, low-density lipoprotein (LDL) cholesterol and body mass index (BMI), but not with disease activity and duration. The activated CD4(+)HLA-DR(+) and CCR5(+) T-cell subsets were expanded in SLE patients. Patients under hydroxychloroquine (HCQ) therapy showed lower CCA-IMT (0.62 ± 0.08 vs. 0.68 ± 0.10 mm; p = 0.03) and better risk-factor profile and presented reduced circulating pro-atherogenic effector memory T-cell subsets and a parallel increased percentage of naïve T-cell subsets. CONCLUSION: HDL represents the main metabolic parameter altered in SLE patients. The increased CCA-IMT in SLE patients may represent the net result of a process in which 'classic' CV risk factors give a continuous contribution, together with immunological factors (CD4(+)HLA-DR(+) T cells) which, on the contrary, could contribute through flares of activity of various degrees over time. Patients under HCQ therapy present a modified metabolic profile, a reduced T-cell activation associated with decreased subclinical atherosclerosis.
BACKGROUND AND AIM: Patients with systemic lupus erythematosus (SLE) have a higher prevalence of subclinical atherosclerosis and higher risk of cardiovascular (CV) events compared to the general population. The relative contribution of CV-, immune- and disease-related risk factors to accelerated atherogenesis in SLE is unclear. METHODS AND RESULTS: Fifty SLE patients with long-lasting disease (mean age 44 ± 10 years, 86% female) and 50 sex- and age-matched control subjects were studied. Common carotid artery intima-media thickness (CCA-IMT) was used as a surrogate marker of atherosclerosis. We evaluated traditional and immune- and disease-related factors, assessed multiple T-cell subsets by 10-parameter-eight-colour polychromatic flow cytometry and addressed the effect of pharmacological therapies on CCA-IMT. In SLE patients, among several cardiometabolic risk factors, only high-density lipoprotein levels (HDL) and their adenosine triphosphate-binding cassette transporter 1 (ABCA-1)-dependent cholesterol efflux capacity were markedly reduced (p < 0.01), whereas the CCA-IMT was significantly increased (p = 0.03) compared to controls. CCA-IMT correlated with systolic blood pressure, low-density lipoprotein (LDL) cholesterol and body mass index (BMI), but not with disease activity and duration. The activated CD4(+)HLA-DR(+) and CCR5(+) T-cell subsets were expanded in SLE patients. Patients under hydroxychloroquine (HCQ) therapy showed lower CCA-IMT (0.62 ± 0.08 vs. 0.68 ± 0.10 mm; p = 0.03) and better risk-factor profile and presented reduced circulating pro-atherogenic effector memory T-cell subsets and a parallel increased percentage of naïve T-cell subsets. CONCLUSION: HDL represents the main metabolic parameter altered in SLE patients. The increased CCA-IMT in SLE patients may represent the net result of a process in which 'classic' CV risk factors give a continuous contribution, together with immunological factors (CD4(+)HLA-DR(+) T cells) which, on the contrary, could contribute through flares of activity of various degrees over time. Patients under HCQ therapy present a modified metabolic profile, a reduced T-cell activation associated with decreased subclinical atherosclerosis.
Authors: T P Mikołajczyk; G Osmenda; B Batko; G Wilk; M Krezelok; D Skiba; T Sliwa; J R Pryjma; T J Guzik Journal: Lupus Date: 2015-08-06 Impact factor: 2.911
Authors: Enrico Ammirati; Francesco Moroni; Giuseppe Danilo Norata; Marco Magnoni; Paolo G Camici Journal: Mediators Inflamm Date: 2015-04-16 Impact factor: 4.711
Authors: Enrico Ammirati; Francesco Moroni; Patrizia Pedrotti; Isabella Scotti; Marco Magnoni; Enrica P Bozzolo; Ornella E Rimoldi; Paolo G Camici Journal: Front Immunol Date: 2014-08-18 Impact factor: 7.561