Associations of Tissue and Soluble LOX-1 with Human Abdominal Aortic Aneurysm.
Anja HofmannYazan KhorzomAnna KlimovaSteffen WolkAlbert BuschPamela SabarstinskiMargarete MüglichDmitry EgorovIrakli KopalianiDavid M PoitzMarvin KapallaBianca HamannFrieda FrankChristian JänichenCoy BrunssenHenning MorawietzChristian ReepsPublished in: Journal of the American Heart Association (2023)
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.
Keyphrases
- low density lipoprotein
- abdominal aortic aneurysm
- peripheral artery disease
- type diabetes
- aortic valve
- coronary artery disease
- smooth muscle
- endothelial cells
- cardiovascular disease
- left ventricular
- healthcare
- pulmonary artery
- heart failure
- cell death
- metabolic syndrome
- poor prognosis
- adipose tissue
- cardiovascular events
- insulin resistance
- coronary artery
- heart rate
- angiotensin converting enzyme
- induced pluripotent stem cells
- pulmonary hypertension
- transcatheter aortic valve replacement
- coronary artery bypass grafting
- resistance training
- human health
- induced apoptosis