title: Treatment with sulphated galactan inhibits macrophage chemotaxis and reduces intraplaque macrophage content in atherosclerotic mice.
abstract: Experimental data from animal models and clinical studies support connections between the haemostasis and inflammation in atherogenesis. These interfaces among inflammation and thrombogenesis have been suggested as targets for pharmacological intervention to reduce disease progression. We hypothesize that the recently discovered antithrombotic drug Sulphated Galactan (SG) (isolated from the red marine alga Acanthophora muscoides) might reduce atherosclerotic plaque vulnerability and inflammatory gene expression in 10-week aged apolipoprotein E deficient (ApoE-/-) mice under high-cholesterol diet for additional 11weeks. Then, the underlying cellular mechanisms were investigated in vitro. SG (10mg/kg) or Vehicle was subcutaneously injected from week 6 until week 11 of the diet. Treatment with SG reduced intraplaque macrophage and Tissue Factor (TF) content as compared to Vehicle-treated animals. Intraplaque TF co-localized and positively correlated with macrophage rich-areas. No changes on atherosclerotic plaque size, and other intraplaque features of vulnerability (such as lipid, neutrophil, MMP-9 and collagen contents) were observed. Moreover, mRNA expression of MMPs, chemokines and genetic markers of Th1/2/reg/17 lymphocyte polarization within mouse aortic arches and spleens was not affected by SG treatment. In vitro, treatment with SG dose-dependently reduced macrophage chemotaxis without affecting TF production. Overall, the chronic SG treatment was well tolerated. In conclusion, our results indicate that SG treatment reduced intraplaque macrophage content (by impacting on cell recruitment) and, concomitantly, intraplaque TF content of potential macrophage origin in atherosclerotic mice.
authors: CAPES Foundation, Ministry of Education of Brazil, Setor Bancário Norte, Quadra 2, Bloco L, Lote 6, 70040-020 Brasília, Brazil; Department of Biochemistry and Molecular Biology, Federal University of Ceará, Avenida Humberto Monte s/n, 60455-760 Fortaleza, Brazil.
authors: Ana Luíza
authors: AL
authors: Gomes Quinderé
authors: Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors: Norma Maria
authors: NM
authors: Barros Benevides
authors: Division of Cardiology, Foundation for Medical Researches, University of Geneva, 64, avenue de la Roseraie, 1211 Geneva, Switzerland.
authors: Graziano
authors: G
authors: Pelli
authors: Division of Cardiology, Foundation for Medical Researches, University of Geneva, 64, avenue de la Roseraie, 1211 Geneva, Switzerland.
authors: Sébastien
authors: S
authors: Lenglet
authors: Division of Cardiology, Foundation for Medical Researches, University of Geneva, 64, avenue de la Roseraie, 1211 Geneva, Switzerland.
authors: Fabienne
authors: F
authors: Burger
authors: Division of Cardiology, Foundation for Medical Researches, University of Geneva, 64, avenue de la Roseraie, 1211 Geneva, Switzerland; First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, viale Benedetto XV, 16132 Genoa, Italy.
authors: Federico
authors: F
authors: Carbone
authors: Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors: Rodrigo A
authors: RA
authors: Fraga-Silva
authors: Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors: Nikolaos
authors: N
authors: Stergiopulos
authors: Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, n4, Gabrielle-Perret-Gentil, 1205 Geneva, Switzerland.
authors: Sabrina
authors: S
authors: Pagano
authors: First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, viale Benedetto XV, 16132 Genoa, Italy.
authors: Maria
authors: M
authors: Bertolotto
authors: First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, viale Benedetto XV, 16132 Genoa, Italy.
authors: Franco
authors: F
authors: Dallegri
authors: Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, n4, Gabrielle-Perret-Gentil, 1205 Geneva, Switzerland.
authors: Nicolas
authors: N
authors: Vuilleumier
authors: Division of Cardiology, Foundation for Medical Researches, University of Geneva, 64, avenue de la Roseraie, 1211 Geneva, Switzerland.
authors: François
authors: F
authors: Mach
authors: Division of Cardiology, Foundation for Medical Researches, University of Geneva, 64, avenue de la Roseraie, 1211 Geneva, Switzerland; First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, viale Benedetto XV, 16132 Genoa, Italy; Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, n4, Gabrielle-Perret-Gentil, 1205 Geneva, Switzerland. Electronic address: fabrizio.montecucco@unige.ch.
authors: Fabrizio
authors: F
authors: Montecucco
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects* / Q000502:physiology; D005685:Galactans / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000187:drug effects* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000473:pathology*; D000461:Rhodophyta
chemical_list: D005685:Galactans; C046510:galactan polysulfate
keywords: Antithrombotic drug; Atherosclerosis; Inflammation; Red alga