Associations of circulating cell-free micro-RNA with vasculopathy and vascular events in SLE patients

S. D. Kay, A. L. Carlsen, Anne Voss, M. K. Poulsen, A. C. P. Diederichsen, N. H. H. Heegaard

Research output: Contribution to journalConference abstract in journalResearchpeer-review

Abstract

Background/Purpose: MicroRNAs (miRNAs) are small noncoding RNAs that modulate protein translation and regulate numerous immunologic and inflammatory pathways. Certain miRNA profiles have been associated with several diseases, including atherosclerosis. Patients with systemic lupus erythematosus (SLE) are known to have a high prevalence of atherosclerosis and a recent study has shown that circulating miRNAs are systematically altered in SLE. Therefore, our objective was to investigate the association between markers of atherosclerosis and cell-free circulating microRNAs in patients with systemic lupus erythematosus. Methods: 120 SLE patients were screened for atherosclerosis by means of cardiac CT demonstrating coronary artery calcification (CAC) and carotid ultrasound visualizing intima-media thickness (IMT) and plaque. Atherosclerosis was defined as either CAC > 99U, carotid IMT>1.00mm and/or carotid plaque. Total RNA was purified from plasma, and 46 specific miRNAs were determined using quantitative real time PCR on a dynamic microfluidic array. Patients with atherosclerosis were compared to those without in terms of expression of cell-free circulating miRNAs. Results: Six miRNAs were expressed differently in plasma from SLE patients with atherosclerosis compared to those without. The expression of miR- 125b, miR-29b-3p, miR-375, miR-101, miR- 122-5p and miR-20a were all decreased in SLE patients with atherosclerosis. Unsupervised hierarchical clustering identified miRNA profiles (an 8-miRNA signature) that differentiated a group of SLE patients from the rest. This patient group (n=16) had significantly increased frequencies of recorded venous thrombotic events (p=0.045), a higher prevalence of beta2- glycoprotein 1 IgG antibodies (p=0.029), and significantly lower platelet counts (p=0.024). Conclusion: Six circulating miRNAs are for the first time shown to be associated with atherosclerosis in a cross-sectional SLE cohort. Furthermore, an 8-miRNA signature was associated with the phenotype of the antiphospholipid syndrome with the patients having a history of venous thrombotic events, beta2-glycoprotein 1 antibodies and lower platelet counts. The findings warrant further prospective studies of the putative association between specific circulating miRNAs and vasculopathy in SLE patients.
Original languageEnglish
Article number3124
JournalArthritis & Rheumatology
Volume67
Issue numberS10
Number of pages2
ISSN2326-5191
DOIs
Publication statusPublished - 2015
EventACR/ARHP: American College of Rheumatology - San Francisco, United States
Duration: 7. Nov 201511. Nov 2015

Conference

ConferenceACR/ARHP
CountryUnited States
CitySan Francisco
Period07/11/201511/11/2015

Cite this

@article{7506407eac284844a4f8b282af2590f0,
title = "Associations of circulating cell-free micro-RNA with vasculopathy and vascular events in SLE patients",
abstract = "Background/Purpose: MicroRNAs (miRNAs) are small noncoding RNAs that modulate protein translation and regulate numerous immunologic and inflammatory pathways. Certain miRNA profiles have been associated with several diseases, including atherosclerosis. Patients with systemic lupus erythematosus (SLE) are known to have a high prevalence of atherosclerosis and a recent study has shown that circulating miRNAs are systematically altered in SLE. Therefore, our objective was to investigate the association between markers of atherosclerosis and cell-free circulating microRNAs in patients with systemic lupus erythematosus. Methods: 120 SLE patients were screened for atherosclerosis by means of cardiac CT demonstrating coronary artery calcification (CAC) and carotid ultrasound visualizing intima-media thickness (IMT) and plaque. Atherosclerosis was defined as either CAC > 99U, carotid IMT>1.00mm and/or carotid plaque. Total RNA was purified from plasma, and 46 specific miRNAs were determined using quantitative real time PCR on a dynamic microfluidic array. Patients with atherosclerosis were compared to those without in terms of expression of cell-free circulating miRNAs. Results: Six miRNAs were expressed differently in plasma from SLE patients with atherosclerosis compared to those without. The expression of miR- 125b, miR-29b-3p, miR-375, miR-101, miR- 122-5p and miR-20a were all decreased in SLE patients with atherosclerosis. Unsupervised hierarchical clustering identified miRNA profiles (an 8-miRNA signature) that differentiated a group of SLE patients from the rest. This patient group (n=16) had significantly increased frequencies of recorded venous thrombotic events (p=0.045), a higher prevalence of beta2- glycoprotein 1 IgG antibodies (p=0.029), and significantly lower platelet counts (p=0.024). Conclusion: Six circulating miRNAs are for the first time shown to be associated with atherosclerosis in a cross-sectional SLE cohort. Furthermore, an 8-miRNA signature was associated with the phenotype of the antiphospholipid syndrome with the patients having a history of venous thrombotic events, beta2-glycoprotein 1 antibodies and lower platelet counts. The findings warrant further prospective studies of the putative association between specific circulating miRNAs and vasculopathy in SLE patients.",
keywords = "*human *American *vascular disease *college *patient *health practitioner *rheumatology atherosclerosis systemic lupus erythematosus carotid artery plasma prevalence thrombocyte count real time polymerase chain reaction arterial wall thickness ultrasound diseases antiphospholipid syndrome coronary artery calcification phenotype prospective study *microRNA *RNA glycoprotein microRNA 125b antibody immunoglobulin G antibody microRNA 20a microRNA 122 microRNA 101 microRNA 375 microRNA 29b marker protein",
author = "Kay, {S. D.} and Carlsen, {A. L.} and Anne Voss and Poulsen, {M. K.} and Diederichsen, {A. C. P.} and Heegaard, {N. H. H.}",
year = "2015",
doi = "10.1002/art.39448",
language = "English",
volume = "67",
journal = "Arthritis & Rheumatology",
issn = "2326-5191",
publisher = "Heinemann",
number = "S10",

}

Associations of circulating cell-free micro-RNA with vasculopathy and vascular events in SLE patients. / Kay, S. D.; Carlsen, A. L.; Voss, Anne; Poulsen, M. K.; Diederichsen, A. C. P.; Heegaard, N. H. H.

In: Arthritis & Rheumatology, Vol. 67, No. S10, 3124, 2015.

Research output: Contribution to journalConference abstract in journalResearchpeer-review

TY - ABST

T1 - Associations of circulating cell-free micro-RNA with vasculopathy and vascular events in SLE patients

AU - Kay, S. D.

AU - Carlsen, A. L.

AU - Voss, Anne

AU - Poulsen, M. K.

AU - Diederichsen, A. C. P.

AU - Heegaard, N. H. H.

PY - 2015

Y1 - 2015

N2 - Background/Purpose: MicroRNAs (miRNAs) are small noncoding RNAs that modulate protein translation and regulate numerous immunologic and inflammatory pathways. Certain miRNA profiles have been associated with several diseases, including atherosclerosis. Patients with systemic lupus erythematosus (SLE) are known to have a high prevalence of atherosclerosis and a recent study has shown that circulating miRNAs are systematically altered in SLE. Therefore, our objective was to investigate the association between markers of atherosclerosis and cell-free circulating microRNAs in patients with systemic lupus erythematosus. Methods: 120 SLE patients were screened for atherosclerosis by means of cardiac CT demonstrating coronary artery calcification (CAC) and carotid ultrasound visualizing intima-media thickness (IMT) and plaque. Atherosclerosis was defined as either CAC > 99U, carotid IMT>1.00mm and/or carotid plaque. Total RNA was purified from plasma, and 46 specific miRNAs were determined using quantitative real time PCR on a dynamic microfluidic array. Patients with atherosclerosis were compared to those without in terms of expression of cell-free circulating miRNAs. Results: Six miRNAs were expressed differently in plasma from SLE patients with atherosclerosis compared to those without. The expression of miR- 125b, miR-29b-3p, miR-375, miR-101, miR- 122-5p and miR-20a were all decreased in SLE patients with atherosclerosis. Unsupervised hierarchical clustering identified miRNA profiles (an 8-miRNA signature) that differentiated a group of SLE patients from the rest. This patient group (n=16) had significantly increased frequencies of recorded venous thrombotic events (p=0.045), a higher prevalence of beta2- glycoprotein 1 IgG antibodies (p=0.029), and significantly lower platelet counts (p=0.024). Conclusion: Six circulating miRNAs are for the first time shown to be associated with atherosclerosis in a cross-sectional SLE cohort. Furthermore, an 8-miRNA signature was associated with the phenotype of the antiphospholipid syndrome with the patients having a history of venous thrombotic events, beta2-glycoprotein 1 antibodies and lower platelet counts. The findings warrant further prospective studies of the putative association between specific circulating miRNAs and vasculopathy in SLE patients.

AB - Background/Purpose: MicroRNAs (miRNAs) are small noncoding RNAs that modulate protein translation and regulate numerous immunologic and inflammatory pathways. Certain miRNA profiles have been associated with several diseases, including atherosclerosis. Patients with systemic lupus erythematosus (SLE) are known to have a high prevalence of atherosclerosis and a recent study has shown that circulating miRNAs are systematically altered in SLE. Therefore, our objective was to investigate the association between markers of atherosclerosis and cell-free circulating microRNAs in patients with systemic lupus erythematosus. Methods: 120 SLE patients were screened for atherosclerosis by means of cardiac CT demonstrating coronary artery calcification (CAC) and carotid ultrasound visualizing intima-media thickness (IMT) and plaque. Atherosclerosis was defined as either CAC > 99U, carotid IMT>1.00mm and/or carotid plaque. Total RNA was purified from plasma, and 46 specific miRNAs were determined using quantitative real time PCR on a dynamic microfluidic array. Patients with atherosclerosis were compared to those without in terms of expression of cell-free circulating miRNAs. Results: Six miRNAs were expressed differently in plasma from SLE patients with atherosclerosis compared to those without. The expression of miR- 125b, miR-29b-3p, miR-375, miR-101, miR- 122-5p and miR-20a were all decreased in SLE patients with atherosclerosis. Unsupervised hierarchical clustering identified miRNA profiles (an 8-miRNA signature) that differentiated a group of SLE patients from the rest. This patient group (n=16) had significantly increased frequencies of recorded venous thrombotic events (p=0.045), a higher prevalence of beta2- glycoprotein 1 IgG antibodies (p=0.029), and significantly lower platelet counts (p=0.024). Conclusion: Six circulating miRNAs are for the first time shown to be associated with atherosclerosis in a cross-sectional SLE cohort. Furthermore, an 8-miRNA signature was associated with the phenotype of the antiphospholipid syndrome with the patients having a history of venous thrombotic events, beta2-glycoprotein 1 antibodies and lower platelet counts. The findings warrant further prospective studies of the putative association between specific circulating miRNAs and vasculopathy in SLE patients.

KW - human American vascular disease college patient health practitioner rheumatology atherosclerosis systemic lupus erythematosus carotid artery plasma prevalence thrombocyte count real time polymerase chain reaction arterial wall thickness ultrasound disease

U2 - 10.1002/art.39448

DO - 10.1002/art.39448

M3 - Conference abstract in journal

VL - 67

JO - Arthritis & Rheumatology

JF - Arthritis & Rheumatology

SN - 2326-5191

IS - S10

M1 - 3124

ER -