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Role of parnaparin in atherosclerosis
Author(s) -
Bonomini Francesca,
Taurone Samanta,
Parnigotto Pierpaolo,
Zamai Loris,
Rodella Luigi F.,
Artico Marco,
Rezzani Rita
Publication year - 2016
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/iep.12217
Subject(s) - inflammation , oxidative stress , vascular smooth muscle , plasminogen activator inhibitor 1 , apolipoprotein b , tumor necrosis factor alpha , endocrinology , plasminogen activator , medicine , biology , smooth muscle , cholesterol
Summary 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.