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

J Am Heart Assoc. 2023 Jul 18;12(14):e027537. doi: 10.1161/JAHA.122.027537. Epub 2023 Jul 8.

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.

Keywords: LOX‐1; abdominal aortic aneurysm; soluble LOX‐1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aortic Aneurysm, Abdominal* / genetics
  • Atherosclerosis*
  • Biomarkers
  • Case-Control Studies
  • Diabetes Mellitus, Type 2*
  • Humans
  • Peripheral Arterial Disease*
  • RNA, Messenger
  • Scavenger Receptors, Class E

Substances

  • Biomarkers
  • RNA, Messenger
  • Scavenger Receptors, Class E
  • OLR1 protein, human