Associations of Tissue and Soluble LOX-1 with Human Abdominal Aortic Aneurysm

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Abstract

Background Indication for prophylactic surgical abdominal aortic aneurysm (AAA) repair depends on the maximal aortic diameter. The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the major receptor for uptake of oxidized low-density lipoprotein cholesterol and is implicated in atherosclerosis. A soluble form of LOX-1 (sLOX-1) has been discussed as a novel biomarker in coronary artery disease and stroke. Herein, we assessed the regulation of aortic LOX-1 as well as the diagnostic and risk stratification potential of sLOX-1 in patients with AAA. Methods and Results Serum sLOX-1 was assessed in a case-control study in AAA (n=104) and peripheral artery disease (n=104). sLOX-1 was not statistically different between AAA and peripheral artery disease but was higher in AAA (β=1.28, P=0.04) after adjusting for age, atherosclerosis, type 2 diabetes, prescription of statins, β-blockers, ACE inhibitors, and therapeutic anticoagulation. sLOX-1 was not associated with the aortic diameter, AAA volume, or the thickness of the intraluminal thrombus. Aortic LOX-1 mRNA expression tended to be higher in AAA when compared with disease, and expression was positively associated with cleaved caspase-3, smooth muscle actin, collagen, and macrophage content. Conclusions In AAA, sLOX-1 was differently affected by age, cardiometabolic diseases, and corresponding medical therapies. Comparison with nonatherosclerotic disease would be beneficial to further elucidate the diagnostic potential of sLOX-1, although it was not useful for risk stratification. Aneurysmal LOX-1 mRNA expression was increased and positively associated with smooth muscle cells and collagen content, suggesting that LOX-1 is eventually not deleterious in human AAA and could counteract AAA rupture.

Details

Original languageEnglish
Article numbere027537
JournalJournal of the American Heart Association
Volume12
Issue number14
Early online date8 Jul 2023
Publication statusPublished - 18 Jul 2023
Peer-reviewedYes

External IDs

unpaywall 10.1161/jaha.122.027537
Scopus 85165221099
Mendeley 45a34a94-f0fa-3b68-96e4-383dec11a79d
ORCID /0000-0001-7803-1972/work/142235127
ORCID /0000-0001-9360-9736/work/164198466

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Keywords

  • Aortic Aneurysm, Abdominal/genetics, Atherosclerosis, Biomarkers, Case-Control Studies, Diabetes Mellitus, Type 2, Humans, Peripheral Arterial Disease, RNA, Messenger, Scavenger Receptors, Class E, soluble LOX-1, LOX-1, abdominal aortic aneurysm

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