Cardiovascular disease in patients with inflammatory rheumatic disease is associated with up-regulation of markers of inflammation in cardiac microvessels and cardiomyocytes.
OBJECTIVE
Various inflammatory rheumatic diseases (IRDs) are associated with increased mortality due to cardiovascular disease. The aim of this study was to investigate heart biopsy specimens obtained from patients undergoing coronary artery bypass grafting and compare markers of inflammation and endothelial cell activation in the cardiac and skeletal muscle of patients with and those without IRD.


METHODS
Paired biopsy specimens of cardiac and skeletal muscle were obtained from 22 consecutive patients with IRD and 8 patients without IRD, all of whom were undergoing coronary artery bypass grafting. The biopsy specimens were evaluated in a blinded manner by conventional microscopy and digital image analysis for cell markers (CD3, CD4, CD8, CD68, CD163, and CD31), HLA (HLA-ABC, HLA-DR, and HLA-DQ), adhesion molecules (intercellular adhesion molecule 1 and vascular cell adhesion molecule 1), and proinflammatory cytokines (interleukin-1alpha, interleukin-1beta, and tumor necrosis factor).


RESULTS
Patients with IRD had significantly higher expression of adhesion molecules, proinflammatory cytokines, and all classes of HLA on cardiomyocytes and endothelial cells but no increase on mononuclear cells in the myocardium compared with patients without IRD. Furthermore, cardiac muscle from patients with IRD displayed significantly higher local expression of inflammation and activation of cardiac microvessels compared with skeletal muscle from the same patients.


CONCLUSIONS
Patients with cardiovascular disease had increased expression of adhesion molecules, HLA, and proinflammatory cytokines in heart tissue, indicating local inflammation involving microvessels and cardiomyocytes that could play a role in the pathogenesis of cardiovascular disease. The more pronounced changes in patients with IRD compared with patients without IRD might contribute to the increased risk of cardiovascular disease and premature death in patients with IRD.
Karolinska University Sola, Karolinska Institutet, Stockholm, Sweden.
Cecilia
C
Grundtman
Ivana
I
Hollan
Oystein T
OT
Førre
Kjell
K
Saatvedt
Knut
K
Mikkelsen
Ingrid E
IE
Lundberg
D015415:Biomarkers / Q000032:analysis; D002318:Cardiovascular Diseases / Q000150:complications* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000032:analysis*; D016207:Cytokines / Q000032:analysis*; D005260:Female; D006680:HLA Antigens / Q000032:analysis*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D055806:Microvessels / Q000737:chemistry*; D018482:Muscle, Skeletal / Q000737:chemistry; D032383:Myocytes, Cardiac / Q000737:chemistry*; D012216:Rheumatic Diseases / Q000150:complications* / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D016207:Cytokines; D006680:HLA Antigens