Syndecan-1 Expression Is Increased in the Aortic Wall of Patients with Type 2 Diabetes but Is Unrelated to Elevated Fasting Plasma Glucagon-Like Peptide-1

Ntika, Stelia; Tracy, Linda; Franco‐Cereceda, Anders; Björck, Hanna M.; Krizhanovskii, Camilla

doi:10.3390/biomedicines9060697

Cited by 5 publications

(9 citation statements)

References 54 publications

(69 reference statements)

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“…In the current study, we report for the first time, by ELISA and histological analysis, that Sdc-1 is one of the members of the PGs overexpressed in human TAA aorta medial layer. Our immunofluorescence analysis showed that Sdc-1 expression is increased not only in media layer, but also in the intima and adventitia layers, in agreement with Ntika et al (30).…”

Section: Discussionsupporting

confidence: 93%

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Syndecan-1 is overexpressed in human thoracic aneurysm but is dispensable for the disease progression in vivo

Zalghout

Arocas

et al. 2021

Preprint

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Glycosaminoglycans (GAGs) pooling has been considered since long as one of the histopathological characteristics defining thoracic aortic aneurysm (TAA) together with smooth muscle cells (SMCs) apoptosis and elastin fibers degradation. However, few information is provided about GAGs composition or potential implication in TAA pathology. Syndecan-1 (Sdc-1) is a heparan sulfate proteoglycan that is implicated in extracellular matrix (ECM) interaction and assembly, regulation of SMCs phenotype and various aspects of inflammation in the vascular wall. In the current work, the regulation of Sdc-1 protein was examined in human TAA by ELISA and immunohistochemistry. In addition, the role of Sdc-1 was evaluated in descending TAA in vivo using a mouse model combining both aortic wall weakening and hypertension. Our results showed that Sdc-1 protein is over expressed in human TAA aortas compared to healthy counterparts and that SMCs are the major cell type expressing Sdc-1. Similarly, in the mouse model used, Sdc-1 expression was increased in TAA aortas compared to healthy samples. Although its protective role against abdominal aneurysm has been reported, we observed that Sdc-1 was dispensable for TAA prevalence or rupture. In addition, Sdc-1 deficiency did not alter the extent of aortic wall dilatation, elastin degradation, collagen deposition, or leukocyte recruitment in our TAA model. These findings suggest that Sdc-1 could be a biomarker revealing TAA pathology. Future investigations could uncover the underlying mechanisms leading to Sdc-1 expression alteration in TAA.

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Section: Discussionsupporting

confidence: 93%

“…RNA level of Sdc-1 (referred previously as syndecan) was previously reported to be increased after vascular injury (29). More recently , an increase of Sdc-1 protein level was observed in the adventitia of human aortas with ascending TAA (30).…”

Section: Discussionmentioning

confidence: 92%

Syndecan-1 is overexpressed in human thoracic aneurysm but is dispensable for the disease progression in vivo

Zalghout

Arocas

et al. 2021

Preprint

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“…Syndecan-1 is a key constituent of glycocalyx on most endothelial cells in the body, and its soluble form is generated by shedding from the endothelial glycocalyx indicative of damage to endothelial cells ( 45 ). As suggested by a previous study ( 18 ), it is possible that increased local shedding of syndecan-1 from the aneurysm is masked by the total pool of the biomarker, resulting in non-significant associations with AA in this study. Furthermore, since we only measured syndecan-1 in plasma and not aortic tissue, this may altogether explain why we do not reproduce the previously found association.…”

Section: Discussionmentioning

confidence: 66%

“…A previous study reported concentrations of syndecan-1, a key constituent of the endothelial glycocalyx and a regulator of inflammation, to be elevated in aortic tissue, though not in plasma, from patients with ascending AA compared to matched controls ( 18 ). Additionally, a study reported elevated syndecan-1 in PLWH compared to uninfected controls ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

Aortic aneurysms and markers of platelet activation, hemostasis, and endothelial disruption in people living with HIV

et al. 2023

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IntroductionPeople living with HIV (PLWH) are at twice the risk of developing cardiovascular diseases and have more than four times higher odds of aortic aneurysm (AA) than the uninfected population. However, biomarkers of AA in PLWH are yet to be discovered. We aimed to investigate whether circulating biomarkers reflecting platelet activation, hemostasis and endothelial disruption, i.e. sCD40L, D-dimer, syndecan-1, and thrombomodulin, were associated with AA in PLWH.MethodsFive hundred seventy one PLWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) study ≥40 years of age with an available contrast-enhanced CT scan as well as available biomarker analyses were included. The biomarkers were analyzed on thawed plasma. For each biomarker, we defined high level as a concentration in the upper quartile and low level as a concentration below the upper quartile. For D-dimer, the cut-off was defined as the lower limit of detection. Using unadjusted and adjusted logistic and linear regression models, we analyzed associations between AA and sCD40L, D-dimer, syndecan-1, and thrombomodulin, respectively in PLWH.ResultsPLWH had median (IQR) age 52 years (47-60), 88% were male, median (IQR) time since HIV diagnosis was 15 years (8-23), and 565 (99%) were currently on antiretroviral treatment. High level of sCD40L was associated with lower odds of AA in both unadjusted (odds ratio, OR, 0.23 (95% CI 0.07-0.77; P=0.017)) and adjusted models (adjusted OR, aOR, 0.23 (95% CI 0.07-0.78; P=0.019)). Detectable level of D-dimer was associated with higher odds of AA in both unadjusted (OR 2.76 (95% CI 1.34-5.67; P=0.006)) and adjusted models (aOR 2.22 (95% CI 1.02-4.85; P=0.045)).ConclusionsSCD40L was associated with lower odds of AA whereas D-dimer was independently associated with higher odds of AA in PLWH. This calls for further investigations into specific biomarkers to aid early diagnosis of AA in PLWH.

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“…The mRNA expression level of SDC-1 (referred previously as syndecan) was previously reported to be increased after vascular injury ( 30 ). More recently, an increase of SDC-1 protein expression was observed in the adventitia of human aortas with ascending TAA ( 31 ).…”

Section: Discussionmentioning

confidence: 95%

Syndecan-1 Is Overexpressed in Human Thoracic Aneurysm but Is Dispensable for the Disease Progression in a Mouse Model

Zalghout

Arocas

et al. 2022

Front. Cardiovasc. Med.

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Glycosaminoglycans (GAGs) pooling has long been considered as one of the histopathological characteristics defining thoracic aortic aneurysm (TAA) together with smooth muscle cells (SMCs) apoptosis and elastin fibers degradation. However, little information is known about GAGs composition or their potential implication in TAA pathology. Syndecan-1 (SDC-1) is a heparan sulfate proteoglycan that is implicated in extracellular matrix (ECM) interaction and assembly, regulation of SMCs phenotype, and various aspects of inflammation in the vascular wall. Therefore, the aim of this study was to determine whether SDC-1 expression was regulated in human TAA and to analyze its role in a mouse model of this disease. In the current work, the regulation of SDC-1 was examined in human biopsies by RT-qPCR, ELISA, and immunohistochemistry. In addition, the role of SDC-1 was evaluated in descending TAA in vivo using a mouse model combining both aortic wall weakening and hypertension. Our results showed that both SDC-1 mRNA and protein are overexpressed in the media layer of human TAA specimens. RT-qPCR experiments revealed a 3.6-fold overexpression of SDC-1 mRNA (p = 0.0024) and ELISA assays showed that SDC-1 protein was increased 2.3 times in TAA samples compared with healthy counterparts (221 ± 24 vs. 96 ± 33 pg/mg of tissue, respectively, p = 0.0012). Immunofluorescence imaging provided evidence that SMCs are the major cell type expressing SDC-1 in TAA media. Similarly, in the mouse model used, SDC-1 expression was increased in TAA specimens compared to healthy samples. Although its protective role against abdominal aneurysm has been reported, we observed that SDC-1 was dispensable for TAA prevalence or rupture. In addition, SDC-1 deficiency did not alter the extent of aortic wall dilatation, elastin degradation, collagen deposition, or leukocyte recruitment in our TAA model. These findings suggest that SDC-1 could be a biomarker revealing TAA pathology. Future investigations could uncover the underlying mechanisms leading to regulation of SDC-1 expression in TAA.

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Syndecan-1 Expression Is Increased in the Aortic Wall of Patients with Type 2 Diabetes but Is Unrelated to Elevated Fasting Plasma Glucagon-Like Peptide-1

Cited by 5 publications

References 54 publications

Syndecan-1 is overexpressed in human thoracic aneurysm but is dispensable for the disease progression in vivo

Syndecan-1 is overexpressed in human thoracic aneurysm but is dispensable for the disease progression in vivo

Aortic aneurysms and markers of platelet activation, hemostasis, and endothelial disruption in people living with HIV

Syndecan-1 Is Overexpressed in Human Thoracic Aneurysm but Is Dispensable for the Disease Progression in a Mouse Model

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