title: Role of parnaparin in atherosclerosis.
abstract: Atherosclerosis is characterized by a proliferation of vascular smooth muscle cells (VSMCs) and their migration to the intima, which induces thickening of the intima itself, but the mechanism remains poorly understood. Low molecular weight heparin (LMWH) inhibits the proliferation of VSMCs. Previous studies have shown that a LMWH, parnaparin (PNP), acts on the processes of atherogenesis and atheroprogression in experimental animal models. The aim of this study was to investigate the involvement of oxidative stress, inflammation and VSMCs in the regulation of vascular wall homeostasis. We also considered the possibility of restoring vascular pathological changes using PNP treatment. In order to evaluate vascular remodelling in this study we have analysed the morphological changes in aortas of an animal model of atherosclerosis, apolipoprotein E-deficient mice (ApoE-/-) fed with a normal or a western diet without treatment or treated with PNP. We also analysed, by immunohistochemistry, the expression of proteins linked to atherogenesis and atheroprogression - an enzyme involved in oxidative stress, iNOS, examples of inflammatory mediators, such as tumour necrosis factor alpha (TNF-α), interleukins 1 and 6 (IL-1 and IL-6), and markers of VSMC changes, in particular plasminogen activator inhibitor-1 and thrombospondin-1 (PAI-1 and TSP-1). Our results could suggest that PNP downregulates VSMC proliferation and migration, mediated by PAI-1 and TSP-1, and reduces inflammation and oxidative stress in vessels. These data suggested that LMWH, in particular PNP, could be a theoretically practical tool in the prevention of atherosclerotic vascular modification.
authors.affiliation: Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bonomini
authors.affiliation: Department of Sensory Organs, Sapienza University of Rome, Rome, Italy.
authors.forename: Samanta
authors.initials: S
authors.lastname: Taurone
authors.affiliation: Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signalling (TES), Onlus, Padua, Italy.
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Parnigotto
authors.affiliation: Department of Earth, Life and Environment Sciences, University of Urbino "Carlo Bo", Urbino, Italy.
authors.forename: Loris
authors.initials: L
authors.lastname: Zamai
authors.affiliation: Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Luigi F
authors.initials: LF
authors.lastname: Rodella
authors.affiliation: Department of Sensory Organs, Sapienza University of Rome, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Artico
authors.affiliation: Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Rezzani
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D006495:Heparin, Low-Molecular-Weight / Q000235:genetics / Q000378:metabolism*; D006965:Hyperplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007249:Inflammation; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D019700:Thrombospondin 1 / Q000378:metabolism; D017539:Tunica Intima / Q000473:pathology; D066253:Vascular Remodeling / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; D006495:Heparin, Low-Molecular-Weight; D018836:Inflammation Mediators; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D019700:Thrombospondin 1; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C080945:parnaparin
keywords: atherosclerosis; intimal hyperplasia; low molecular weight heparin; parnaparin