Relevance of Heparan Sulfate and Heparanase to Severity of COVID-19 in the Elderly
The prevalence of arterial and venous thrombosis markedly rises with age. The annual rate of venous thromboembolism (VTE) is estimated at 1/100 patients above 80 years of age. While aging is associated with some changes in the levels of coagulation proteins and activation markers, this does not explain the exponential increase in VTE risk observed in octogenarians.
Accordingly, such findings may be attributed to several factors. It has been recently demonstrated that coagulant activity under flow is mainly controlled by residual tissue factor (TF)/collagen and endothelial glycocalyx. Given that the vessel wall is a major player in hemostasis, endothelial dysfunction, which increases with age, likely contributes to the development of thrombosis in cardiovascular diseases. Rapidly growing evidence links particulate air pollution exposure with an increased risk of respiratory and cardiovascular disease. In the coronavirus disease 2019 (COVID-19) pandemic, the elderly are particularly vulnerable to severe vascular complications, including deep vein thrombosis and pulmonary embolism. This population appears to be particularly exposed in certain densely populated and air-polluted urban areas.
11 January 2021 (online)
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- 1 Martinelli I. Risk factors in venous thromboembolism. Thromb Haemost 2001; 86 (01) 395-403
- 2 Tofler GH, Massaro J, Levy D. et al. Relation of the prothrombotic state to increasing age (from the Framingham Offspring Study). Am J Cardiol 2005; 96 (09) 1280-1283
- 3 Mari D, Mannucci PM, Coppola R, Bottasso B, Bauer KA, Rosenberg RD. Hypercoagulability in centenarians: the paradox of successful aging. Blood 1995; 85 (11) 3144-3149
- 4 Brouns SLN, Provenzale I, van Geffen JP, van der Meijden PEJ, Heemskerk JWM. Localized endothelial-based control of platelet aggregation and coagulation under flow: a proof-of-principle vessel-on-a-chip study. J Thromb Haemost 2020; 18 (04) 931-941
- 5 Mannucci PM, Harari S, Martinelli I, Franchini M. Effects on health of air pollution: a narrative review. Intern Emerg Med 2015; 10 (06) 657-662
- 6 Lemaitre M, Carrat F, Rey G, Miller M, Simonsen L, Viboud C. Mortality burden of the 2009 A/H1N1 influenza pandemic in France: comparison to seasonal influenza and the A/H3N2 pandemic. PLoS One 2012; 7 (09) e45051
- 7 Ginaldi L, Loreto MF, Corsi MP, Modesti M, De Martinis M. Immunosenescence and infectious diseases. Microbes Infect 2001; 3 (10) 851-857
- 8 Leng J, Goldstein DR. Impact of aging on viral infections. Microbes Infect 2010; 12 (14-15): 1120-1124
- 9 Cambier J. Immunosenescence: a problem of lymphopoiesis, homeostasis, microenvironment, and signaling. Immunol Rev 2005; 205: 5-6
- 10 Nikolich-Zugich J. Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections. Nat Rev Immunol 2008; 8 (07) 512-522
- 11 Frasca D, Riley RL, Blomberg BB. Humoral immune response and B-cell functions including immunoglobulin class switch are downregulated in aged mice and humans. Semin Immunol 2005; 17 (05) 378-384
- 12 Ademokun A, Wu YC, Dunn-Walters D. The ageing B cell population: composition and function. Biogerontology 2010; 11 (02) 125-137
- 13 Liu WM, van der Zeijst BA, Boog CJ, Soethout EC. Aging and impaired immunity to influenza viruses: implications for vaccine development. Hum Vaccin 2011; 7 (Suppl): 94-98
- 14 Le Saux S, Weyand CM, Goronzy JJ. Mechanisms of immunosenescence: lessons from models of accelerated immune aging. Ann N Y Acad Sci 2012; 1247: 69-82
- 15 Cavanagh MM, Weyand CM, Goronzy JJ. Chronic inflammation and aging: DNA damage tips the balance. Curr Opin Immunol 2012; 24 (04) 488-493
- 16 Gutter-Kapon L, Alishekevitz D, Shaked Y. et al. Heparanase is required for activation and function of macrophages. Proc Natl Acad Sci U S A 2016; 113 (48) E7808-E7817
- 17 Digre A, Singh K, Åbrink M. et al. Overexpression of heparanase enhances T lymphocyte activities and intensifies the inflammatory response in a model of murine rheumatoid arthritis. Sci Rep 2017; 7: 46229
- 18 Konno K, Arai H, Motomiya M. et al. A biochemical study on glycosaminoglycans (mucopolysaccharides) in emphysematous and in aged lungs. Am Rev Respir Dis 1982; 126 (05) 797-801
- 19 Iriyama S, Matsunaga Y, Takahashi K, Matsuzaki K, Kumagai N, Amano S. Activation of heparanase by ultraviolet B irradiation leads to functional loss of basement membrane at the dermal-epidermal junction in human skin. Arch Dermatol Res 2011; 303 (04) 253-261
- 20 Nitschmann E, Berry L, Bridge S. et al. Morphological and biochemical features affecting the antithrombotic properties of the aorta in adult rabbits and rabbit pups. Thromb Haemost 1998; 79 (05) 1034-1040
- 21 Nitschmann E, Berry L, Bridge S. et al. Morphologic and biochemical features affecting the antithrombotic properties of the inferior vena cava of rabbit pups and adult rabbits. Pediatr Res 1998; 43 (01) 62-67
- 22 Campisi J. Aging, tumor suppression and cancer: high wire-act!. Mech Ageing Dev 2005; 126 (01) 51-58
- 23 Bochenek ML, Bauer T, Gogiraju R. et al. The endothelial tumor suppressor p53 is essential for venous thrombus formation in aged mice. Blood Adv 2018; 2 (11) 1300-1314
- 24 Zhang H, Newman DR, Bonner JC, Sannes PL. Over-expression of human endosulfatase-1 exacerbates cadmium-induced injury to transformed human lung cells in vitro. Toxicol Appl Pharmacol 2012; 265 (01) 27-42