Circulating Levels of the Heparan Sulfate Proteoglycan Syndecan-4 Positively Associate with Blood Pressure in Healthy Premenopausal Women.

Gary R Hunter,Maria De Luca,David R Bryan

doi:10.3390/biom11030342

Gary R Hunter, Maria De Luca + Show 1 more

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https://doi.org/10.3390/biom11030342

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Journal: Biomolecules	Publication Date: Feb 24, 2021
Citations: 6	License type: CC BY 4.0

Affiliation: University of Alabama at Birmingham

Abstract

Syndecans (SDCs) are transmembrane proteins that are present on most cell types where they play a role in multiple physiological processes, including cell–matrix adhesion and inflammation. Growing evidence suggests that elevated levels of both shed SDC1 and SDC4 are associated with hypertension and cardiovascular diseases, but their relationships with cardiovascular risk factors in healthy individuals are unknown. The primary objective of this study was to investigate whether serum levels of SDC4 and SDC1 were associated with body composition, hemodynamic parameters, pro-inflammatory cytokine concentrations, and urinary noradrenaline and dopamine levels in healthy women (17 African American and 20 European American) between the ages of 20 and 40 years old. Univariate analyses revealed only a significant (p < 0.05) inverse correlation between serum SDC1 and body fat percentage. On the other hand, serum SDC4 was positively correlated with systolic blood pressure, diastolic blood pressure, and urinary levels of noradrenaline and dopamine. Serum SDC4 was also a significant predictor of systolic blood pressure in a multivariate regression model that included fat-free mass and urinary dopamine levels as significant independent variables. The result did not change even adjusting for race. Our findings indicate that SDC4 has an important role in the physiological regulation of blood pressure.

Highlights

Syndecans (SDCs) are type-I transmembrane glycoproteins belonging to the family of heparan sulfate proteoglycans that include cell-surface glycosylphosphatidylinositolanchored proteins and secreted proteoglycans found in basement membranes [1]
The analysis revealed that serum SDC4 remained significantly associated with Systolic blood pressure (SBP) levels after adjusting for body composition variables or for fat-free mass (FFM) and urinary DA levels
The correlations observed in our study are in the low to moderate range, the findings corroborate the involvement of SDC4 in blood pressure regulation as previously seen by Lipphard and colleagues [19], who revealed that patients with resistant hypertension had significantly higher serum SDC4 levels than healthy controls

Summary

Introduction

Syndecans (SDCs) are type-I transmembrane glycoproteins belonging to the family of heparan sulfate proteoglycans that include cell-surface glycosylphosphatidylinositolanchored proteins (glypicans) and secreted proteoglycans found in basement membranes (agrin, collagen XVIII, and perlecan) [1]. All SDCs are characterized by an extracellular domain (ectodomain) with attachment sites for glycosaminoglycan (GAG) chains (e.g., heparan sulfate and chondroitin sulfate) that mediate interactions with a wide array of ligands, such as extracellular matrix components, soluble growth factors, morphogens, chemokines, and cytokines [1]. The ectodomain of all SDCs is constitutively released from the cell surface by proteolytic cleavage in a process known as ectodomain shedding that is mediated by matrix metalloproteinases [3]. SDCs contain a highly conserved transmembrane domain and a short cytoplasmic tail [1]. It is through their cytoplasmic domain, which includes binding sites for cytoskeletal proteins and protein kinases, that members of the Biomolecules 2021, 11, 342.

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