Circulating soluble low-density lipoprotein receptor-related protein 1 (sLRP1) concentration is associated with hypercholesterolemia: A new potential biomarker for atherosclerosis. (15th December 2015)

• Record Type: Journal Article
• Authors: de Gonzalo-Calvo, D.; Cenarro, A.; Martínez-Bujidos, M.; Badimon, L.; Bayes-Genis, A.; Ordonez-Llanos, J.; Civeira, F.; Llorente-Cortés, V.
• Is Part Of: International journal of cardiology. Volume 201(2015)
• Page Start: 20
• Page End: 29
• Publication Date: 2015-12-15
• Subjects: Atherosclerosis -- Biomarker -- Hypercholesterolemia -- Soluble low-density lipoprotein receptor-related protein 1 -- Vascular smooth muscle cell; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2015.07.085
• Languages: English
• ISSNs: 0167-5273

Abstract

Abstract: Background: There is clinical interest in identifying novel lipid biomarkers for evaluating cardiovascular risk and targeting lipid-lowering treatment. Low-density lipoprotein receptor-related protein 1 (LRP1) plays a crucial role in the dysregulated cholesterol transfer from modified lipoproteins to human coronary vascular smooth muscle cells (hVSMCs), promoting hVSMC-derived foam cell formation. LRP1 has a soluble and circulating form (sLRP1) generated from LRP1. Cholesterol modulates the release of the soluble form of LRP1. Using in vitro, ex vivo and patient-based approaches, we tested the association between circulating sLRP1 concentrations and hypercholesterolemia and the potential of sLRP1 as a biomarker of atherosclerosis. Methods and results: Circulating sLRP1 concentrations were higher in severe hypercholesterolemia compared to moderate hypercholesterolemia or normocholesterolemia (Study 1). Circulating sLRP1 was significantly associated with established pro-atherogenic lipid parameters in two different hypercholesterolemic populations (Studies 2 and 3). sLRP1 concentrations decreased after statin treatment and increased after statin withdrawal (Study 3). In vitro experiments showed that native LDL, aggregated LDL and VLDL + IDL lipoproteins induced the release of sLRP1 from hVSMC. sLRP1 levels were increased in the conditioned medium of coronary atherosclerotic plaque areas extracted from patients compared to non-atherosclerotic areas of the same coronary artery and patient. Circulating sLRP1 concentrations were independently associated with the occurrence of carotid atherosclerosis in a hypercholesterolemic population (Study 2). The later association was higher than that observed for other classical or novel lipid parameters. Conclusions: Circulating sLRP1 is a new lipid-related parameter potentially useful as a biomarker for atherosclerosis.