Leukotriene B4 levels in human atherosclerotic plaques and abdominal aortic aneurysms.
BACKGROUND
Leukotriene B4 (LTB4) has been associated with the initiation and progression of atherosclerosis and abdominal aortic aneurysm (AAA) formation. However, associations of LTB4 levels with tissue characteristics and adverse clinical outcome of advanced atherosclerosis and AAA are scarcely studied. We hypothesized that LTB4 levels are associated with a vulnerable plaque phenotype and adverse clinical outcome. Furthermore, that LTB4 levels are associated with inflammatory AAA and adverse clinical outcome.


METHODS
Atherosclerotic plaques and AAA specimens were selected from two independent databases for LTB4 measurements. Plaques were isolated during carotid endarterectomy from asymptomatic (n = 58) or symptomatic (n = 317) patients, classified prior to surgery. LTB4 levels were measured without prior lipid extraction and levels were corrected for protein content. LTB4 levels were related to plaque phenotype, baseline patient characteristics and clinical outcome within three years following surgery. Seven non-diseased mammary artery specimens served as controls. AAA specimens were isolated during open repair, classified as elective (n = 189), symptomatic (n = 29) or ruptured (n = 23). LTB4 levels were measured similar to the plaque measurements and were related to tissue characteristics, baseline patient characteristics and clinical outcome. Twenty-six non-diseased aortic specimens served as controls.


RESULTS
LTB4 levels corrected for protein content were not significantly associated with histological characteristics specific for vulnerable plaques or inflammatory AAA as well as clinical presentation. Moreover, it could not predict secondary manifestations independently investigated in both databases. However, LTB4 levels were significantly lower in controls compared to plaque (p = 0.025) or AAA (p = 0.017).


CONCLUSIONS
LTB4 levels were not associated with a vulnerable plaque phenotype or inflammatory AAA or clinical presentation. This study does not provide supportive evidence for a role of LTB4 in atherosclerotic plaque destabilization or AAA expansion. However, these data should be interpreted with care, since LTB4 measurements were performed without prior lipid extractions.
Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Pleunie
P
van den Borne
Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands ; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.
Sander W
SW
van der Laan
Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands ; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.
Sandra M
SM
Bovens
Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
Dave
D
Koole
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
Mark C
MC
Kowala
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
Laura F
LF
Michael
Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands ; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.
Arjan H
AH
Schoneveld
Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Sander M
SM
van de Weg
Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Evelyn
E
Velema
Department of Vascular Surgery, Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands.
Jean-Paul
JP
de Vries
Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
Gert J
GJ
de Borst
Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
Frans L
FL
Moll
Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands ; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands ; Cardiovascular Research Institute and Surgery, National University Hospital Singapore, Singapore, Singapore.
Dominique P V
DP
de Kleijn
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands ; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Paul H A
PH
Quax
Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands ; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.
Imo E
IE
Hoefer
Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands ; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.
Gerard
G
Pasterkamp
D000704:Analysis of Variance; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism*; D016022:Case-Control Studies; D006801:Humans; D007150:Immunohistochemistry; D007975:Leukotriene B4 / Q000097:blood / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000378:metabolism*
D007975:Leukotriene B4