D de Gonzalo-Calvo1, A Cenarro2, M Martínez-Bujidos3, L Badimon1, A Bayes-Genis4, J Ordonez-Llanos5, F Civeira2, V Llorente-Cortés6. 1. Cardiovascular Research Center, CSIC-ICCC, IIB-SantPau, Barcelona, Spain. 2. Lipid Unit and Molecular Research Laboratory, IIS Aragón, Hospital Universitario Miguel Servet, Zaragoza, Spain. 3. Biochemistry Department, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain. 4. Cardiology Service, Germans Trias i Pujol University Hospital, Badalona, Spain. 5. Biochemistry Department, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain; Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. 6. Cardiovascular Research Center, CSIC-ICCC, IIB-SantPau, Barcelona, Spain. Electronic address: cllorente@csic-iccc.org.
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.
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.
Authors: Ricardo Gamboa; María José Jaramillo-Estrella; María Del Rocio Martínez-Alvarado; Maria Elena Soto; Yazmin Estela Torres-Paz; David de Gonzalo-Calvo; Leonardo Del Valle-Mondragón; Rebeca López-Marure; Vicenta C Llorente-Cortés; Claudia Huesca-Gómez Journal: Arq Bras Cardiol Date: 2021-01 Impact factor: 2.000
Authors: Santiago Roura; Carolina Gálvez-Montón; David de Gonzalo-Calvo; Ana Gámez Valero; Paloma Gastelurrutia; Elena Revuelta-López; Cristina Prat-Vidal; Carolina Soler-Botija; Aida Llucià-Valldeperas; Isaac Perea-Gil; Oriol Iborra-Egea; Francesc E Borràs; Josep Lupón; Vicenta Llorente-Cortés; Antoni Bayes-Genis Journal: J Cell Mol Med Date: 2017-05-29 Impact factor: 5.310
Authors: David de Gonzalo-Calvo; Cristina Colom; David Vilades; Andrea Rivas-Urbina; Abdel-Hakim Moustafa; Montserrat Pérez-Cuellar; Jose Luis Sánchez-Quesada; Antonio Pérez; Vicenta LLorente-Cortes Journal: Sci Rep Date: 2018-01-18 Impact factor: 4.379