Human IgM Antibodies to Malondialdehyde Conjugated With Albumin Are Negatively Associated With Cardiovascular Disease Among 60‐Year‐Olds

Autor: Karin Leander, Max Vikström, Anna G. Frostegård, Ulf de Faire, Mizanur Rahman, Anquan Liu, Johan Frostegård, Divya Thiagarajan, Bruna Gigante, Sudhir Singh, Roman A. Zubarev, Bo Zhang, Susanna L. Lundström, Mai-Lis Hellénius
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
cardiovascular disease risk factors
Epidemiology
Myocardial Infarction
Coronary Disease
030204 cardiovascular system & hematology
Gastroenterology
Angina
0302 clinical medicine
cardiovascular disease
Interquartile range
antibody
Clinical Studies
Hyperlipidemia
Mechanisms
Prospective Studies
Myocardial infarction
Original Research
biology
Incidence
Middle Aged
Hospitalization
Stroke
Cardiovascular Diseases
Female
Antibody
Cardiology and Cardiovascular Medicine
malondialdehyde
medicine.medical_specialty
oxidation
Enzyme-Linked Immunosorbent Assay
Angina Pectoris
03 medical and health sciences
proteomics
Internal medicine
medicine
Humans
Serum Albumin
Aged
Autoantibodies
Sweden
business.industry
Type 2 Diabetes Mellitus
Odds ratio
medicine.disease
immune system
030104 developmental biology
Endocrinology
Immunoglobulin M
Case-Control Studies
biology.protein
business
Biomarkers
Basic Science Research
Follow-Up Studies
Lipoprotein
Zdroj: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
ISSN: 2047-9980
DOI: 10.1161/jaha.116.004415
Popis: Background Malondialdehyde ( MDA ) is generated during lipid peroxidation as in oxidized low‐density lipoprotein, but antibodies against oxidized low‐density lipoprotein show variable results in clinical studies. We therefore studied the risk of cardiovascular disease ( CVD ) associated with IgM antibodies against MDA conjugated with human albumin (anti‐ MDA ). Methods and Results In a 5‐ to 7‐year follow‐up of 60‐year‐old men and women from Stockholm County previously screened for cardiovascular risk factors (2039 men, 2193 women), 209 incident CVD cases (defined as new events of coronary heart disease, fatal and nonfatal myocardial infarction, ischemic stroke, and hospitalization for angina pectoris) and 620 age‐ and sex‐matched controls were tested for IgM anti‐ MDA by ELISA . Antibody peptide/protein characterization was done using a proteomics de novo sequencing approach. After adjustment for smoking, body‐mass index, type 2 diabetes mellitus, hyperlipidemia, and hypertension, an increased CVD risk was observed in the low IgM anti‐ MDA percentiles (below 10th and 25th) (odds ratio and 95% CI : 2.0; 1.19–3.36 and 1.67; 1.16–2.41, respectively). Anti‐ MDA above the 66th percentile was associated with a decreased CVD risk (odds ratio 0.68; CI : 0.48–0.98). After stratification by sex, associations were only present among men. IgM anti‐ MDA levels were lower among cases (median [interquartile range]: 141.0 [112.7–164.3] versus 147.4 [123.5–169.6]; P =0.0177), even more so among men (130.6 [107.7–155.3] versus 143.0 [120.1–165.2]; P =0.001). The IgM anti‐ MDA variable region profiles are distinctly different and also more homologous in their content (correlates strongly with fewer peptides) than control antibodies (not binding MDA ). Conclusions IgM anti‐ MDA is a protection marker for CVD . This finding could have diagnostic and therapeutic implications.
Databáze: OpenAIRE
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