Syndecan-4 as a Marker of Endothelial Dysfunction in Patients with Resistant Hypertension

Abstract

(1) Background: Arterial hypertension (HTN) is one of the most relevant cardiovascular risk factors. Nowadays multiple pharmaceutical treatment options exist with novel interventional methods (e.g., baroreflex activation therapy (BAT)) as a last resort to treat patients with resistant HTN. Although pathophysiology behind resistant HTN is still not fully understood. There is evidence that selected biomarkers may be involved in the pathophysiology of HTN. (2) Methods: We investigated serum SDC4-levels in patients suffering from resistant HTN before and 6 months after BAT implantation. We collected 19 blood samples from patients with resistant HTN and blood pressure above target and measured serum SDC4-levels. (3) Results: Our results showed high serum SDC4-levels in patients with resistant HTN as compared to a healthy population. Patients with both, resistant HTN and diabetes mellitus type II, demonstrated higher serum SDC4-levels. β-blockers had lowering effects on serum SDC4-levels, whereas calcium channel blockers were associated with higher levels of serum SDC4. BAT implantation did not lead to a significant difference in serum SDC4-levels after 6 months of therapy. (4) Conclusion: Based on our results we propose SDC4 is elevated in patients suffering from resistant HTN. Thus, SDC4 might be a potential marker for endothelial dysfunction in patients with resistant hypertension.

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

“…The primary finding of the present study is that elevated levels of serum SDC4 significantly correlate with increased SBP and DBP as well as 24-h urine NE and DA in a cohort of healthy premenopausal women. Although 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. Moreover, the relationship between SBP, serum SDC4, and catecholamine levels is in agreement with results from the same study, which further showed that βblockers had lowering effects on serum SDC4 levels of hypertensive patients [19].…”

“…Although 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. Moreover, the relationship between SBP, serum SDC4, and catecholamine levels is in agreement with results from the same study, which further showed that βblockers had lowering effects on serum SDC4 levels of hypertensive patients [19]. It is well-established that catecholamines regulate blood pressure [34].…”

“…A growing body of evidence indicates that SDC1 is released into the circulation in response to endothelial injury [14,15] and elevated levels of serum SDC1 have been detected in patients with severe sepsis [16] and have been associated with adverse clinical outcomes in patients with ischemic heart failure [17]. More recent studies have also shown positive associations of SDC4 levels with coronary heart disease in women [18] and with resistant hypertension [19]. Together, these findings suggest that circulating SDC1 and SDC4 levels could be useful predictive markers of eGC damage in selected pathologies [17,18,20].…”

“…As such, a secondary objective of this study was to determine whether variability in SDC4 and/or SDC1 might contribute to the racial disparity in blood pressure levels. Finally, given that serum SDC4 levels have been positively associated with hypertension [19] and exercise training has been shown to have beneficial effects on blood pressure arterial stiffness [27], another aim was to investigate the effect of long-term aerobic exercise on the abundance of circulating SDC4.…”

Bioinformatics analysis of potential key genes and mechanisms in type 2 diabetes mellitus

“…CCL20 [188], CRH (corticotropin releasing hormone) [189], SPP1 [190], LDLR (low density lipoprotein receptor) [191], RORA (RAR related orphan receptor A) [192], LYZ (lysozyme) [193], PTPRN2 [194], DAPK2 [195], OIP5 [196], PON3 [197], NR4A3 [198], VCAN (versican) [199], CNTNAP2 [200], IL1RAP [201], GLI2 [202], CDH13 [203], AEBP1 [204], BGN (biglycan) [205], LOX (lysyl oxidase) [206], IL1RL1 [207] and LUM (lumican) [208] were found to be involved in advancement of obesity, but these genes might be key for development of T2DM. C4BPA [209], KYNU (kynureninase) [210], ORM1 [211], ARSA (arylsulfatase A) [212], CYB5R3 [213], MAT1A [214], SDC4 [215], ASL (argininosuccinate lyase) [216], SLC4A4 [217], EPHB6 [218], SPARCL1 [219], THBS2 [220], EFNB2 [221] and CD248 [222] were revealed to be associated with hypertension, but these genes might be involved in progression of T2DM. GSDMD (gasdermin D) [223], UNC5B [224] and PDGFB (platelet derived growth factor subunit B) [225] have been reported significantly expressed in diabetic nephropathy.…”