PMID- 34320837
OWN - NLM
STAT- MEDLINE
DCOM- 20210913
LR  - 20210913
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 41
IP  - 9
DP  - 2021 Sep
TI  - Anti-dsDNA Antibodies Increase the Cardiovascular Risk in Systemic Lupus 
      Erythematosus Promoting a Distinctive Immune and Vascular Activation.
PG  - 2417-2430
LID - 10.1161/ATVBAHA.121.315928 [doi]
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is associated to boosted 
      atherosclerosis development and a higher cardiovascular disease risk. This study 
      aimed to delineate the role of anti-double stranded DNA (anti-dsDNA) antibodies 
      on the molecular profile and the activity of immune and vascular cells, as well 
      as on their enhanced cardiovascular risk. APPROACH AND RESULTS: Eighty SLE 
      patients were included. Extensive clinical/analytical evaluation was performed, 
      including cardiovascular disease parameters (endothelial function, proatherogenic 
      dyslipidemia, and carotid intima-media thickness). Gene and protein expression 
      profiles were evaluated in monocytes from patients diagnosed positive or negative 
      for anti-dsDNA antibodies by using NanoString and cytokine arrays, respectively. 
      NETosis and circulating inflammatory profile was assessed in both neutrophils and 
      plasma. Positivity and persistence of anti-dsDNA antibodies in SLE patients were 
      associated to endothelial dysfunction, proatherogenic dyslipidemia, and 
      accelerated atherosclerosis. In parallel, anti-dsDNA antibodies were linked to 
      the aberrant activation of innate immune cells, so that anti-dsDNA(+) SLE 
      monocytes showed distinctive gene and protein expression/activity profiles, and 
      neutrophils were more prone to suffer NETosis in comparison with anti-dsDNA(-) 
      patients. Anti-dsDNA(+) patients further displayed altered levels of numerous 
      circulating mediators related to inflammation, NETosis, and cardiovascular risk. 
      In vitro, Ig-dsDNA promoted NETosis on neutrophils, apoptosis on monocytes, 
      modulated the expression of inflammation and thrombosis-related molecules, and 
      induced endothelial activation, at least partially, by FcR (Fc receptor)-binding 
      mechanisms. CONCLUSIONS: Anti-dsDNA antibodies increase the cardiovascular risk 
      of SLE patients by altering key molecular processes that drive a distinctive and 
      coordinated immune and vascular activation, representing a potential tool in the 
      management of this comorbidity.
FAU - Patino-Trives, Alejandra Maria
AU  - Patino-Trives AM
AD  - Rheumatology Service (A.M.P.-T., C.P.-S., L.P.-S., M.L.-T., M.C.A.-A., L.A.-R., 
      I.A.-d.l.R., C.R.-R., P.F., N.B., A.E.-C., E.C.-E., M.A.A.-Z., C.L.-P.), Reina 
      Sofia Hospital/Maimonides Institute for Research in Biomedicine of 
      Cordoba/University of Cordoba, Spain.
FAU - Perez-Sanchez, Carlos
AU  - Perez-Sanchez C
AD  - Rheumatology Service (A.M.P.-T., C.P.-S., L.P.-S., M.L.-T., M.C.A.-A., L.A.-R., 
      I.A.-d.l.R., C.R.-R., P.F., N.B., A.E.-C., E.C.-E., M.A.A.-Z., C.L.-P.), Reina 
      Sofia Hospital/Maimonides Institute for Research in Biomedicine of 
      Cordoba/University of Cordoba, Spain.
AD  - Deparment of Cell Biology, Immunology and Physiology, University of Cordoba, 
      Campus de Excelencia Internacional Agroalimentario ceiA3, Spain (C.P.-S., 
      J.A.G.-R., J.M.V.).
FAU - Perez-Sanchez, Laura
AU  - Perez-Sanchez L
AD  - Rheumatology Service (A.M.P.-T., C.P.-S., L.P.-S., M.L.-T., M.C.A.-A., L.A.-R., 
      I.A.-d.l.R., C.R.-R., P.F., N.B., A.E.-C., E.C.-E., M.A.A.-Z., C.L.-P.), Reina 
      Sofia Hospital/Maimonides Institute for Research in Biomedicine of 
      Cordoba/University of Cordoba, Spain.
FAU - Luque-Tevar, Maria
AU  - Luque-Tevar M
AD  - Rheumatology Service (A.M.P.-T., C.P.-S., L.P.-S., M.L.-T., M.C.A.-A., L.A.-R., 
      I.A.-d.l.R., C.R.-R., P.F., N.B., A.E.-C., E.C.-E., M.A.A.-Z., C.L.-P.), Reina 
      Sofia Hospital/Maimonides Institute for Research in Biomedicine of 
      Cordoba/University of Cordoba, Spain.
FAU - Abalos-Aguilera, M Carmen
AU  - Abalos-Aguilera MC
AD  - Rheumatology Service (A.M.P.-T., C.P.-S., L.P.-S., M.L.-T., M.C.A.-A., L.A.-R., 
      I.A.-d.l.R., C.R.-R., P.F., N.B., A.E.-C., E.C.-E., M.A.A.-Z., C.L.-P.), Reina 
      Sofia Hospital/Maimonides Institute for Research in Biomedicine of 
      Cordoba/University of Cordoba, Spain.
FAU - Alcaide-Ruggiero, Lourdes
AU  - Alcaide-Ruggiero L
AD  - Rheumatology Service (A.M.P.-T., C.P.-S., L.P.-S., M.L.-T., M.C.A.-A., L.A.-R., 
      I.A.-d.l.R., C.R.-R., P.F., N.B., A.E.-C., E.C.-E., M.A.A.-Z., C.L.-P.), Reina 
      Sofia Hospital/Maimonides Institute for Research in Biomedicine of 
      Cordoba/University of Cordoba, Spain.
FAU - Arias-de la Rosa, Ivan
AU  - Arias-de la Rosa I
AD  - Rheumatology Service (A.M.P.-T., C.P.-S., L.P.-S., M.L.-T., M.C.A.-A., L.A.-R., 
      I.A.-d.l.R., C.R.-R., P.F., N.B., A.E.-C., E.C.-E., M.A.A.-Z., C.L.-P.), Reina 
      Sofia Hospital/Maimonides Institute for Research in Biomedicine of 
      Cordoba/University of Cordoba, Spain.
FAU - Roman-Rodriguez, Cristobal
AU  - Roman-Rodriguez C
AD  - Rheumatology Service (A.M.P.-T., C.P.-S., L.P.-S., M.L.-T., M.C.A.-A., L.A.-R., 
      I.A.-d.l.R., C.R.-R., P.F., N.B., A.E.-C., E.C.-E., M.A.A.-Z., C.L.-P.), Reina 
      Sofia Hospital/Maimonides Institute for Research in Biomedicine of 
      Cordoba/University of Cordoba, Spain.
FAU - Segui, Pedro
AU  - Segui P
AD  - Radiology Service (P.S.), Reina Sofia Hospital/Maimonides Institute for Research 
      in Biomedicine of Cordoba/University of Cordoba, Spain.
FAU - Espinosa, Mario
AU  - Espinosa M
AD  - Nephrology Service (M.E.), Reina Sofia Hospital/Maimonides Institute for Research 
      in Biomedicine of Cordoba/University of Cordoba, Spain.
FAU - Font, Pilar
AU  - Font P
AD  - Rheumatology Service (A.M.P.-T., C.P.-S., L.P.-S., M.L.-T., M.C.A.-A., L.A.-R., 
      I.A.-d.l.R., C.R.-R., P.F., N.B., A.E.-C., E.C.-E., M.A.A.-Z., C.L.-P.), Reina 
      Sofia Hospital/Maimonides Institute for Research in Biomedicine of 
      Cordoba/University of Cordoba, Spain.
FAU - Barbarroja, Nuria
AU  - Barbarroja N
AD  - Rheumatology Service (A.M.P.-T., C.P.-S., L.P.-S., M.L.-T., M.C.A.-A., L.A.-R., 
      I.A.-d.l.R., C.R.-R., P.F., N.B., A.E.-C., E.C.-E., M.A.A.-Z., C.L.-P.), Reina 
      Sofia Hospital/Maimonides Institute for Research in Biomedicine of 
      Cordoba/University of Cordoba, Spain.
FAU - Escudero-Contreras, Alejandro
AU  - Escudero-Contreras A
AD  - Rheumatology Service (A.M.P.-T., C.P.-S., L.P.-S., M.L.-T., M.C.A.-A., L.A.-R., 
      I.A.-d.l.R., C.R.-R., P.F., N.B., A.E.-C., E.C.-E., M.A.A.-Z., C.L.-P.), Reina 
      Sofia Hospital/Maimonides Institute for Research in Biomedicine of 
      Cordoba/University of Cordoba, Spain.
FAU - Antonio Gonzalez-Reyes, Jose
AU  - Antonio Gonzalez-Reyes J
AD  - Deparment of Cell Biology, Immunology and Physiology, University of Cordoba, 
      Campus de Excelencia Internacional Agroalimentario ceiA3, Spain (C.P.-S., 
      J.A.G.-R., J.M.V.).
FAU - Manuel Villalba, Jose
AU  - Manuel Villalba J
AD  - Deparment of Cell Biology, Immunology and Physiology, University of Cordoba, 
      Campus de Excelencia Internacional Agroalimentario ceiA3, Spain (C.P.-S., 
      J.A.G.-R., J.M.V.).
FAU - Collantes-Estevez, Eduardo
AU  - Collantes-Estevez E
AD  - Rheumatology Service (A.M.P.-T., C.P.-S., L.P.-S., M.L.-T., M.C.A.-A., L.A.-R., 
      I.A.-d.l.R., C.R.-R., P.F., N.B., A.E.-C., E.C.-E., M.A.A.-Z., C.L.-P.), Reina 
      Sofia Hospital/Maimonides Institute for Research in Biomedicine of 
      Cordoba/University of Cordoba, Spain.
FAU - Aguirre-Zamorano, M Angeles
AU  - Aguirre-Zamorano MA
AD  - Rheumatology Service (A.M.P.-T., C.P.-S., L.P.-S., M.L.-T., M.C.A.-A., L.A.-R., 
      I.A.-d.l.R., C.R.-R., P.F., N.B., A.E.-C., E.C.-E., M.A.A.-Z., C.L.-P.), Reina 
      Sofia Hospital/Maimonides Institute for Research in Biomedicine of 
      Cordoba/University of Cordoba, Spain.
FAU - Lopez-Pedrera, Chary
AU  - Lopez-Pedrera C
AD  - Rheumatology Service (A.M.P.-T., C.P.-S., L.P.-S., M.L.-T., M.C.A.-A., L.A.-R., 
      I.A.-d.l.R., C.R.-R., P.F., N.B., A.E.-C., E.C.-E., M.A.A.-Z., C.L.-P.), Reina 
      Sofia Hospital/Maimonides Institute for Research in Biomedicine of 
      Cordoba/University of Cordoba, Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210729
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Antibodies, Antinuclear)
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Lipids)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adult
MH  - Antibodies, Antinuclear/*blood
MH  - Apoptosis
MH  - Biomarkers/blood
MH  - Cardiovascular Diseases/blood/diagnostic imaging/genetics/*immunology
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Cross-Sectional Studies
MH  - Cytokines/genetics/metabolism
MH  - DNA/*immunology
MH  - Endothelial Cells/*immunology/metabolism
MH  - Extracellular Traps/metabolism
MH  - Female
MH  - Heart Disease Risk Factors
MH  - Humans
MH  - Immunoglobulin G/*blood
MH  - Leukocytes/*immunology/metabolism
MH  - Lipids/blood
MH  - Lupus Erythematosus, Systemic/blood/diagnosis/genetics/*immunology
MH  - Male
MH  - Middle Aged
MH  - Monocytes/immunology/metabolism
MH  - Neutrophils/immunology/metabolism
MH  - Oxidative Stress
MH  - Retrospective Studies
MH  - Risk Assessment
MH  - Signal Transduction
OTO - NOTNLM
OT  - anti-dsDNA antibodies
OT  - comorbidity
OT  - lupus erythematosus, systemic
OT  - plasma
OT  - risk factors
EDAT- 2021/07/30 06:00
MHDA- 2021/09/14 06:00
CRDT- 2021/07/29 05:29
PHST- 2021/07/30 06:00 [pubmed]
PHST- 2021/09/14 06:00 [medline]
PHST- 2021/07/29 05:29 [entrez]
AID - 10.1161/ATVBAHA.121.315928 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2021 Sep;41(9):2417-2430. doi: 
      10.1161/ATVBAHA.121.315928. Epub 2021 Jul 29.