Dual roles of heparanase in human carotid plaque calcification

Aldi, Silvia; Eriksson, Linnéa; Kronqvist, Malin; Lengquist, Mariette; Löfling, Marie; Folkersen, Lasse; Matic, Ljubica; Maegdefessel, Lars; Grinnemo, Karl‐Henrik; Li, Jin Ping; Österholm, Cecilia; Hedin, Ulf

doi:10.1016/j.atherosclerosis.2018.12.027

Cited by 15 publications

(7 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The functional role of HPSE in cardiovascular disease has been especially investigated in the context of vascular injury: indeed, HPSE has been shown to be a critical mediator of thrombosis following angioplasty and stent-induced flow disturbance [15]. Aldi and colleagues in this issue of Atherosclerosis elegantly show that HPSE may have dual functions in vascular calcification, depending on the stage of the disease and the presence of inflammatory cells [16]: while HPSE plausibly enhances mineralization and osteogenic differentiation of vascular smooth muscle cells, it is associated with inflammation-induced osteoclast differentiation and activity in advanced atherosclerotic plaques.…”

Section: Mechanistic Roles Of Hpse In Human Diseasementioning

confidence: 99%

Heparanase in health and disease: The neglected housekeeper of the cell?

Shu

Santulli

2019

Atherosclerosis

View full text Add to dashboard Cite

Section: Mechanistic Roles Of Hpse In Human Diseasementioning

confidence: 99%

Heparanase in health and disease: The neglected housekeeper of the cell?

Shu

Santulli

2019

Atherosclerosis

View full text Add to dashboard Cite

“…Mechanistic studies on heparanase action have focused primarily on its expression by tumor cells and revealed that heparanase promotes an aggressive tumor behavior via multiple mechanisms. However, non-tumor (host) cells including T lymphocytes, B lymphocytes, neutrophils, monocyte/macrophages, endothelial cells, osteoclasts, and fibroblasts can also upregulate heparanase expression upon activation and thereby contribute not only to cancer progression (Edovitsky et al., 2004, Arvatz et al., 2011b, Lerner et al., 2011, Vlodavsky et al., 2012, Barash et al., 2014, Ramani et al., 2016), but also to acute and chronic inflammation (Li et al., 2008, Vlodavsky et al., 2012, Goldberg et al., 2013), autoimmunity (de Mestre et al., 2007, Li et al., 2008), atherosclerosis (Vlodavsky et al., 2013, Aldi et al., 2019), tissue fibrosis (Secchi et al., 2015), kidney dysfunction (van den Hoven et al., 2007, Garsen et al., 2016a, Garsen et al., 2016b), ocular surface dysfunction (McKown et al., 2009, Zhang et al., 2010b), diabetes (Parish et al., 2013), and diabetic complications (Gil et al., 2012, Wang et al., 2013).…”

Section: Discussionmentioning

confidence: 99%

Targeting Heparanase in Cancer: Inhibition by Synthetic, Chemically Modified, and Natural Compounds

et al. 2019

View full text Add to dashboard Cite

Heparanase is an endoglycosidase involved in remodeling the extracellular matrix and thereby in regulating multiple cellular processes and biological activities. It cleaves heparan sulfate (HS) side chains of HS proteoglycans into smaller fragments and hence regulates tissue morphogenesis, differentiation, and homeostasis. Heparanase is overexpressed in various carcinomas, sarcomas, and hematological malignancies, and its upregulation correlates with increased tumor size, tumor angiogenesis, enhanced metastasis, and poor prognosis. In contrast, knockdown or inhibition of heparanase markedly attenuates tumor progression, further underscoring the potential of anti-heparanase therapy. Heparanase inhibitors were employed to interfere with tumor progression in preclinical studies, and selected heparin mimetics are being examined in clinical trials. However, despite tremendous efforts, the discovery of heparanase inhibitors with high clinical benefit and minimal adverse effects remains a therapeutic challenge. This review discusses the key roles of heparanase in cancer progression focusing on the status of natural, chemically modified, and synthetic heparanase inhibitors in various types of malignancies.

show abstract

“…101 In a later study, heparanase expression was observed in osteoclast-like cells in endarterectomy samples, suggesting demineralization; however, in an in vitro study, human carotid smooth muscle cells with increased heparanase expression showed increased mineralization and osteogenic differentiation suggesting increased calcification. 102 The authors suggest that in the developing plaque, heparanase may contribute to mineralization, but in the advanced plaque, and in the presence of inflammatory mediators, heparanase may be involved in osteolysis. Heparanase increased activated factor X generation in the presence of tissue factor from the damaged or inflamed vascular wall, suggesting a procoagulant effect.…”

Section: Heart and Large Vesselsmentioning

confidence: 99%

Heparan Sulfate Proteoglycans in Diabetes

Hiebert

2021

Semin Thromb Hemost

View full text Add to dashboard Cite

Diabetes is a complex disorder responsible for the mortality and morbidity of millions of individuals worldwide. Although many approaches have been used to understand and treat diabetes, the role of proteoglycans, in particular heparan sulfate proteoglycans (HSPGs), has only recently received attention. The HSPGs are heterogeneous, highly negatively charged, and are found in all cells primarily attached to the plasma membrane or present in the extracellular matrix (ECM). HSPGs are involved in development, cell migration, signal transduction, hemostasis, inflammation, and antiviral activity, and regulate cytokines, chemokines, growth factors, and enzymes. Hyperglycemia, accompanying diabetes, increases reactive oxygen species and upregulates the enzyme heparanase that degrades HSPGs or affects the synthesis of the HSPGs altering their structure. The modified HSPGs in the endothelium and ECM in the blood vessel wall contribute to the nephropathy, cardiovascular disease, and retinopathy seen in diabetes. Besides the blood vessel, other cells and tissues in the heart, kidney, and eye are affected by diabetes. Although not well understood, the adipose tissue, intestine, and brain also reveal HSPG changes associated with diabetes. Further, HSPGs are significantly involved in protecting the β cells of the pancreas from autoimmune destruction and could be a focus of prevention of type I diabetes. In some circumstances, HSPGs may contribute to the pathology of the disease. Understanding the role of HSPGs and how they are modified by diabetes may lead to new treatments as well as preventative measures to reduce the morbidity and mortality associated with this complex condition.

show abstract

Dual roles of heparanase in human carotid plaque calcification

Cited by 15 publications

References 46 publications

Heparanase in health and disease: The neglected housekeeper of the cell?

Heparanase in health and disease: The neglected housekeeper of the cell?

Targeting Heparanase in Cancer: Inhibition by Synthetic, Chemically Modified, and Natural Compounds

Heparan Sulfate Proteoglycans in Diabetes

Contact Info

Product

Resources

About