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

D. De Gonzalo-Calvo, A. Cenarro, M. Martínez-Bujidos, L. Badimon, A. Bayes-Genis, J. Ordonez-Llanos, F. Civeira, V. Llorente-Cortés

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Abstract

© 2015 Elsevier Ireland Ltd. 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.
Original languageEnglish
Pages (from-to)20-29
JournalInternational Journal of Cardiology
Volume201
DOIs
Publication statusPublished - 10 Oct 2015

Keywords

  • Atherosclerosis
  • Biomarker
  • Hypercholesterolemia
  • Soluble low-density lipoprotein receptor-related protein 1
  • Vascular smooth muscle cell

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    De Gonzalo-Calvo, D., Cenarro, A., Martínez-Bujidos, M., Badimon, L., Bayes-Genis, A., Ordonez-Llanos, J., Civeira, F., & Llorente-Cortés, V. (2015). Circulating soluble low-density lipoprotein receptor-related protein 1 (sLRP1) concentration is associated with hypercholesterolemia: A new potential biomarker for atherosclerosis. International Journal of Cardiology, 201, 20-29. https://doi.org/10.1016/j.ijcard.2015.07.085