Hyperglycemia-induced effects on glycocalyx components in the retina

Chen

Front. Cardiovasc. Med.

et al. 2022

BackgroundThe endothelial glycocalyx (EG) is essential for maintaining microvascular homeostasis. However, the relationship between the EG and coronary microcirculation remains to be elucidated. One of the main components of EG is syndecan-1, and its shedding has been claimed to represent the state of the EG. In this study, we aimed to analyze the association between syndecan-1 and the coronary microcirculation.MethodsWe enrolled suspected coronary artery disease (CAD) patients who consecutively underwent coronary angiography (CAG) and angiography-based analysis of physiological indices in the left anterior descending artery (LAD). Serum syndecan-1 was measured by enzyme-linked immunosorbent assay (ELISA). The coronary microcirculation was evaluated by the presence of coronary microvascular dysfunction (CMD) and an impaired microvascular vasodilatory capacity (IMVC), which were quantified by an angiography-derived index of microcirculatory resistance (IMRangio) in the maximum hyperemic state (H-IMRangio) induced by adenosine triphosphate and the ratio (RRRangio) of IMRangio in the non-hyperemic phase to H-IMRangio, respectively.ResultsA total of 528 patients were enrolled in this study. There was no difference in epicardial coronary complexity between patients with high syndecan-1 (HSG) and low syndecan-1 (LSG) levels grouped by the median concentration of syndecan-1 (SYNTAX: 7[3, 10] vs. 9[4, 12], P = 0.15). However, H-IMRangio and RRRangio were different between the LSG and HSG groups (H-IMRangio: 23.64 ± 6.28 vs. 27.67 ± 5.59, P < 0.01; RRRangio: 1.74[1.46, 2.08] vs. 1.55[1.34, 1.72], P < 0.01). Patients with CMD (H-IMRangio > 25) and patients with IMVC (RRRangio below the median value) both had higher syndecan-1 levels (CMD: 86.44 ± 54.15 vs. 55.2 ± 43.72, P < 0.01; IMVC: 83.86 ± 55.41 vs. 59.68 ± 45.06, P < 0.01). After adjustment for confounding factors, HSG remained associated with the presence of CMD and IMVC (CMD: odds ratio [OR]: 2.769, P < 0.01; IMVC: OR: 1.908, P < 0.01).ConclusionHigh levels of syndecan-1 are independently associated with the presence of CMD and IMVC among patients with suspected CAD.

Section: Resultsmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Association of endothelial glycocalyx shedding and coronary microcirculation assessed by an angiography-derived index of microcirculatory resistance in patients with suspected coronary artery disease

Chen

Front. Cardiovasc. Med.

et al. 2022

“…During the early stages of kidney disease, one of the most characteristic alterations is the dysfunction of the glomerular endothelium and the loss of the glycocalyx, a layer of protective molecules covering the endothelial cells lining the blood vessels, including those in the kidneys [ 52 , 53 ]. The disruption or shedding of the glycocalyx has been associated with numerous inflammatory conditions, including DKD [ 21 , 54 ]. Our research also found that inflammation in the kidneys of diabetic nephropathy mice is exacerbated, and there is severe shedding of the glycocalyx in the glomerular endothelium.…”

Section: Discussionmentioning

confidence: 99%

Endothelial CXCR2 deficiency attenuates renal inflammation and glycocalyx shedding through NF-κB signaling in diabetic kidney disease

Cui,

Chen,

et al. 2024

Cell Commun Signal

Background The incidence of diabetic kidney disease (DKD) continues to rapidly increase, with limited available treatment options. One of the hallmarks of DKD is persistent inflammation, but the underlying molecular mechanisms of early diabetic kidney injury remain poorly understood. C-X-C chemokine receptor 2 (CXCR2), plays an important role in the progression of inflammation-related vascular diseases and may bridge between glomerular endothelium and persistent inflammation in DKD. Methods Multiple methods were employed to assess the expression levels of CXCR2 and its ligands, as well as renal inflammatory response and endothelial glycocalyx shedding in patients with DKD. The effects of CXCR2 on glycocalyx shedding, and persistent renal inflammation was examined in a type 2 diabetic mouse model with Cxcr2 knockout specifically in endothelial cells (DKD-Cxcr2eCKO mice), as well as in glomerular endothelial cells (GECs), cultured in high glucose conditions. Results CXCR2 was associated with early renal decline in DKD patients, and endothelial-specific knockout of CXCR2 significantly improved renal function in DKD mice, reduced inflammatory cell infiltration, and simultaneously decreased the expression of proinflammatory factors and chemokines in renal tissue. In DKD conditions, glycocalyx shedding was suppressed in endothelial Cxcr2 knockout mice compared to Cxcr2L/L mice. Modulating CXCR2 expression also affected high glucose-induced inflammation and glycocalyx shedding in GECs. Mechanistically, CXCR2 deficiency inhibited the activation of NF-κB signaling, thereby regulating inflammation, restoring the endothelial glycocalyx, and alleviating DKD. Conclusions Taken together, under DKD conditions, activation of CXCR2 exacerbates inflammation through regulation of the NF-κB pathway, leading to endothelial glycocalyx shedding and deteriorating renal function. Endothelial CXCR2 deficiency has a protective role in inflammation and glycocalyx dysfunction, suggesting its potential as a promising therapeutic target for DKD treatment.

“…Indeed, long-term hyperglycemia activates numerous metabolic pathways involved in the production of reactive oxygen species (ROS) and pro-inflammatory mediators, which are in turn associated to leukostasis, disruption of cell-cell junctions, loss of endothelial cells and pericytes, and breakdown of the blood-retinal barrier BRB, resulting in vascular dysfunction, neurodegeneration and microglia activation [16]. In addition, hyperglycemia promotes the dysfunction and loss of the endothelial glycocalyx contributing to the increase in vascular permeability, capillary occlusion and leukostasis, and, thus potentially to atherothrombotic processes and DR progression [17,18]. The concomitant complement hyperactivation and the accumulation of immune cells and pro-inflammatory molecules into the retina due to the BRB breakdown contribute to DR progression further promoting retinal neurovascular damage and local chronic low-grade inflammation [19].…”

Section: Brief Overview On the Pathogenesis Of Diabetic Retinopathymentioning

confidence: 99%

Diabetic Retinopathy: Soluble and Imaging Ocular Biomarkers

Ferrara

Loda

Coco

et al. 2023

JCM

Diabetic retinopathy (DR), the most common microvascular complication of diabetes mellitus, represents the leading cause of acquired blindness in the working-age population. Due to the potential absence of symptoms in the early stages of the disease, the identification of clinical biomarkers can have a crucial role in the early diagnosis of DR as well as for the detection of prognostic factors. In particular, imaging techniques are fundamental tools for screening, diagnosis, classification, monitoring, treatment planning and prognostic assessment in DR. In this context, the identification of ocular and systemic biomarkers is crucial to facilitate the risk stratification of diabetic patients; moreover, reliable biomarkers could provide prognostic information on disease progression as well as assist in predicting a patient’s response to therapy. In this context, this review aimed to provide an updated and comprehensive overview of the soluble and anatomical biomarkers associated with DR.