Marit D Solbu1, Svein O Kolset2, Trond G Jenssen3, Tom Wilsgaard4, Maja-Lisa Løchen4, Ellisiv B Mathiesen5, Toralf Melsom6, Bjørn O Eriksen6, Trine M Reine2. 1. Section of Nephrology, University Hospital of North Norway, Tromsø, Norway; Metabolic and Renal Research Group, UiT The Arctic University of Norway, Tromsø, Norway. Electronic address: marit.solbu@unn.no. 2. Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway. 3. Metabolic and Renal Research Group, UiT The Arctic University of Norway, Tromsø, Norway; Department of Transplant Medicine, Oslo University Hospital, Oslo, Norway. 4. Epidemiology of Chronic Diseases Research Group, UiT The Arctic University of Norway, Tromsø, Norway. 5. Brain and Circulation Research Group, UiT The Arctic University of Norway, Tromsø, Norway; Neurological Department, University Hospital of North Norway, Tromsø, Norway. 6. Section of Nephrology, University Hospital of North Norway, Tromsø, Norway; Metabolic and Renal Research Group, UiT The Arctic University of Norway, Tromsø, Norway.
Abstract
BACKGROUND AND AIMS: Cardiovascular disease is a common cause of morbidity and mortality, with gender differences in pathophysiology. The endothelial glycocalyx maintains vascular integrity, and glycocalyx shedding reflects endothelial dysfunction and early atherosclerosis. Syndecan-1 and -4 are components of the glycocalyx, and increased serum levels indicate glycocalyx damage. We hypothesised that increased serum syndecan-1 and -4 were independently associated with myocardial infarction (MI), ischaemic stroke and all-cause mortality in men and women from a general population. METHODS: Using a case-cohort design, we included 1495 participants from the Tromsø Study 2001-02. Syndecan-1 and -4 were measured in serum. Baseline variables also included age, gender, cardiovascular risk factors and urinary albumin-creatinine ratio (ACR). Hazard ratios were assessed using multivariable Cox regression models. RESULTS: Between baseline in 2001-02 and December 2007 fatal or non-fatal MI was experienced by 328 and ischaemic stroke by 191 subjects, and 423 participants died. Syndecan-4 was independently associated with MI (hazard ratio per 10 ng/mL increase 1.32; 95% confidence interval 1.06-1.63), but not ischaemic stroke and mortality, and the associations were unchanged by adjustment for urinary ACR. Interaction between syndecan-4 and sex was borderline significant, and in gender-specific analysis, syndecan-4 was associated with MI in women only. Syndecan-1 was not associated with any endpoint. CONCLUSIONS: Syndecan-4 was associated with incident MI, and the association was stronger in women than in men. This suggests a link between endothelial glycocalyx shedding and coronary heart disease in women. Use of syndecan-4 as a risk marker in clinical setting needs further investigation.
BACKGROUND AND AIMS: Cardiovascular disease is a common cause of morbidity and mortality, with gender differences in pathophysiology. The endothelial glycocalyx maintains vascular integrity, and glycocalyx shedding reflects endothelial dysfunction and early atherosclerosis. Syndecan-1 and -4 are components of the glycocalyx, and increased serum levels indicate glycocalyx damage. We hypothesised that increased serum syndecan-1 and -4 were independently associated with myocardial infarction (MI), ischaemic stroke and all-cause mortality in men and women from a general population. METHODS: Using a case-cohort design, we included 1495 participants from the Tromsø Study 2001-02. Syndecan-1 and -4 were measured in serum. Baseline variables also included age, gender, cardiovascular risk factors and urinary albumin-creatinine ratio (ACR). Hazard ratios were assessed using multivariable Cox regression models. RESULTS: Between baseline in 2001-02 and December 2007 fatal or non-fatal MI was experienced by 328 and ischaemic stroke by 191 subjects, and 423 participants died. Syndecan-4 was independently associated with MI (hazard ratio per 10 ng/mL increase 1.32; 95% confidence interval 1.06-1.63), but not ischaemic stroke and mortality, and the associations were unchanged by adjustment for urinary ACR. Interaction between syndecan-4 and sex was borderline significant, and in gender-specific analysis, syndecan-4 was associated with MI in women only. Syndecan-1 was not associated with any endpoint. CONCLUSIONS:Syndecan-4 was associated with incident MI, and the association was stronger in women than in men. This suggests a link between endothelial glycocalyx shedding and coronary heart disease in women. Use of syndecan-4 as a risk marker in clinical setting needs further investigation.
Authors: Thea Parsberg Støle; Marianne Lunde; Xin Shen; Marita Martinsen; Per Kristian Lunde; Jia Li; Francesca Lockwood; Ivar Sjaastad; William Edward Louch; Jan Magnus Aronsen; Geir Christensen; Cathrine Rein Carlson Journal: Front Cell Dev Biol Date: 2022-08-25
Authors: Maria De Luca; Denise Vecchie'; Baskaran Athmanathan; Sreejit Gopalkrishna; Jennifer A Valcin; Telisha M Swain; Rogerio Sertie; Kennedy Wekesa; Glenn C Rowe; Shannon M Bailey; Prabhakara R Nagareddy Journal: Nutrients Date: 2019-11-18 Impact factor: 5.717