Claudia Stefanutti1, Livia Pisciotta2, Elda Favari3, Serafina Di Giacomo4, Federica Vacondio3, Maria Grazia Zenti5, Claudia Morozzi4, Daniele Berretti6, Dario Mesce4, Marco Vitale4, Andrea Pasta7, Annalisa Ronca8, Anna Garuti7, Matteo Manfredini9, Eduardo Anglés-Cano10, Santica Marija Marcovina11, Gerald Francis Watts12. 1. Department of Molecular Medicine, Lipid Clinic and Atherosclerosis Prevention Centre, 'Umberto I' Hospital - 'Sapienza' University of Rome, Rome, Italy. Electronic address: claudia.stefanutti@uniroma1.it. 2. Department of Internal Medicine - Polyclinic Hospital San Martino, University of Genoa, Genoa, Italy. 3. Department of Food and Drug, University of Parma, Parma, Italy. 4. Department of Molecular Medicine, Lipid Clinic and Atherosclerosis Prevention Centre, 'Umberto I' Hospital - 'Sapienza' University of Rome, Rome, Italy. 5. Endocrinology and Metabolic Diseases, Civile Maggiore Hospital of Verona, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy. 6. Immunohematology and Transfusion Medicine, ASL3, Pistoia, Italy. 7. Department of Internal Medicine, University of Genoa, Italy. 8. Department of Food and Drug, University of Parma, Parma, Italy; Endocrinology and Metabolic Diseases, Civile Maggiore Hospital of Verona, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy. 9. Department of Life Sciences, University of Parma, Italy. 10. Inserm UMR_S1140 "Innovative Therapies in Haemostasis" Faculté de Pharmacie de Paris, Université Paris Descartes, Paris, France; French Institute of Health and Medical Research (Inserm), France. 11. Department of Medicine, Northwest Lipid Research Laboratories, University of Washington, Seattle, WA, USA. 12. School of Medicine, Faculty of Health and Medical Sciences - Cardiometabolic Service, Department of Cardiology, Royal Perth Hospital University of Western Australia, Perth, Western Australia, Australia.
Abstract
BACKGROUND: Coronary artery disease (CAD) risk is greater with higher plasma lipoprotein(a)[Lp(a)] concentrations or smaller apoisoform size and putatively with increased cellular cholesterol loading capacity (CLC). The relationship between Lp(a) and CLC is not known. Information on Lp(a) polymorphisms in Italian patients is lacking. OBJECTIVE: The objective of this study was to determine relationships between Lp(a) and CLC, the impact of lipoprotein apheresis (LA), and describe the genetic profile of Lp(a). METHODS: We conducted a multicenter, observational study in Italian patients with hyperLp(a) and premature CAD with (n = 18)/without (n = 16) LA in which blood samples were analyzed for Lp(a) parameter and CLC. Genetic profiling of LPA was conducted in patient receiving LA. RESULTS: Mean macrophage CLC of the pre-LA serum was significantly higher than that of normolipidemic controls (19.7 ± 0.9 μg/mg vs 16.01 ± 0.98 μg/mg of protein, respectively). After LA, serum macrophage CLC was markedly lower relative to preapheresis (16.1 ± 0.8 μg/mg protein; P = .003) and comparable with CLC of the normolipidemic serum. LA did not significantly affect average apo(a) isoform size distribution. No anthropometric or lipid parameters studied were related to serum CLC, but there was a relationship between CLC and the Lp(a) plasma concentration (P = .035). DNA analysis revealed a range of common genetic variants. Two rare, new variants were identified: LPA exon 21, c.3269C>G, p.Pro1090Arg, and rs41259144 p.Arg990Gln, c.2969G>A CONCLUSIONS: LA reduces serum Lp(a) and also reduces macrophage CLC. Novel genetic variants of the LPA gene were identified, and geographic variations were noted. The complexity of these polymorphisms means that genetic assessment is not a predictor of CAD risk in hyperLp(a).
BACKGROUND:Coronary artery disease (CAD) risk is greater with higher plasma lipoprotein(a)[Lp(a)] concentrations or smaller apoisoform size and putatively with increased cellular cholesterol loading capacity (CLC). The relationship between Lp(a) and CLC is not known. Information on Lp(a) polymorphisms in Italian patients is lacking. OBJECTIVE: The objective of this study was to determine relationships between Lp(a) and CLC, the impact of lipoprotein apheresis (LA), and describe the genetic profile of Lp(a). METHODS: We conducted a multicenter, observational study in Italian patients with hyperLp(a) and premature CAD with (n = 18)/without (n = 16) LA in which blood samples were analyzed for Lp(a) parameter and CLC. Genetic profiling of LPA was conducted in patient receiving LA. RESULTS: Mean macrophage CLC of the pre-LA serum was significantly higher than that of normolipidemic controls (19.7 ± 0.9 μg/mg vs 16.01 ± 0.98 μg/mg of protein, respectively). After LA, serum macrophage CLC was markedly lower relative to preapheresis (16.1 ± 0.8 μg/mg protein; P = .003) and comparable with CLC of the normolipidemic serum. LA did not significantly affect average apo(a) isoform size distribution. No anthropometric or lipid parameters studied were related to serum CLC, but there was a relationship between CLC and the Lp(a) plasma concentration (P = .035). DNA analysis revealed a range of common genetic variants. Two rare, new variants were identified: LPA exon 21, c.3269C>G, p.Pro1090Arg, and rs41259144 p.Arg990Gln, c.2969G>A CONCLUSIONS: LA reduces serum Lp(a) and also reduces macrophage CLC. Novel genetic variants of the LPA gene were identified, and geographic variations were noted. The complexity of these polymorphisms means that genetic assessment is not a predictor of CAD risk in hyperLp(a).
Authors: Santica M Marcovina; Noémie Clouet-Foraison; Marlys L Koschinsky; Mark S Lowenthal; Allen Orquillas; Michael B Boffa; Andrew N Hoofnagle; Tomáš Vaisar Journal: Clin Chem Date: 2021-03-01 Impact factor: 12.167
Authors: Jun-Xu Gu; Juan Huang; Shan-Shan Li; Li-Hua Zhou; Ming Yang; Yang Li; Ai-Min Zhang; Yue Yin; Na Zhang; Mei Jia; Ming Su Journal: Sci Rep Date: 2022-03-04 Impact factor: 4.379
Authors: George Athanasios Karpouzas; Bianca Papotti; Sarah Ormseth; Marcella Palumbo; Elizabeth Hernandez; Maria Pia Adorni; Francesca Zimetti; Matthew Budoff; Nicoletta Ronda Journal: RMD Open Date: 2022-09