Increased RhoA/Rho-Kinase Activity and Markers of Endothelial Dysfunction in Young Adult Subjects with Metabolic Syndrome

Leguina-Ruzzi, Alberto; Pereira, Jaime; Pereira-Flores, Karla; Valderas, Juan P.; Mezzano, Diego; Velarde, Victoria; Sáez, Claudia G.

doi:10.1089/met.2015.0061

Cited by 23 publications

(11 citation statements)

References 44 publications

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“…It has been shown that insulin resistance can start from an early age, 51 thereby increasing the predisposition for complications associated with diabetes in the later years of life. The clinical management of the complications of T2D is therefore an important public health issue; more work on this topic is required in the future.…”

Section: Resultsmentioning

confidence: 99%

BLT2 expression improves skin integrity and protects from alterations caused by hyperglycemia in type 2 diabetes

Leguina-Ruzzi

Valderas

2016

Dermato-Endocrinology

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Type 2 diabetes (T2D) can go undiagnosed for years, leading to a stage where chronic high blood sugar produces complications such as delayed wound healing. Reports have shown that BLT2 activation improves keratinocyte migration and wound healing, as well as protecting the epidermal barrier through the promotion of actin polymerization.The goal of this study was to elucidate the role of BLT2 expression in skin epithelial integrity in T2D.For this purpose, we used both wild type (WT) and BLT2 knockout mice in a model, in which a T2D-like phenotype was induced by keeping the animals on a high fat (HF) diet over 5 weeks. In a parallel in vitro approach, we cultured BLT2-transfected HaCaT cells at both low and high glucose concentrations for 48 h. Structure, transepithelial resistance (TEER), IL-1ß, IL-8 or CXCL2, MMP9, Filaggrin, Loricrin and Keratin 10 (K10) were evaluated ex vivo and in vitro. Additionally, wound healing (WH) was studied in vitro.The skin from T2D and BLT2 knockout mice showed a reduction in TEER and the expression of IL-1ß, and in increase in CXCL2, MMP9, Filaggrin, Loricrin and K10 expression. The structure suggested an atrophic epidermis; however, the skin was dramatically affected in the BLT2 knockout mice kept on a HF diet.HaCaT-BLT2 cells presented as an organized monolayer and showed higher TEER and wound healing compared with vector only-transfected HaCaT-Mock cells. Likewise, alterations in the expression of skin inflammatory, matrix degradation and differentiation markers under low and high glucose conditions were less severe than in HaCaT-Mock cells.Our results suggest that BLT2 improves epithelial integrity and function by regulating differentiation markers, cytokines and MMP9. Furthermore, BLT2 attenuates the damaging effects of high glucose levels, thereby accelerating wound healing.

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Section: Resultsmentioning

confidence: 99%

BLT2 expression improves skin integrity and protects from alterations caused by hyperglycemia in type 2 diabetes

Leguina-Ruzzi

Valderas

2016

Dermato-Endocrinology

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“…Breakdown of triglycerides has been shown to elicit proinflammatory responses in endothelial cells through activation of toll-like receptors and NFkβ (26,27). Notably, in resemblance to our OSAS patients, in patients with metabolic syndrome, but without diabetes mellitus or hypertension, elevated levels of interleukin-6, soluble CD40L, monocyte chemoattractant protein and CRP have been found to be associated with altered ROCK activity (28). Moreover, both statins and specific ROCK pathway inhibitors such as fasudil reduce atherosclerosis risk through their parallel actions on lipid metabolism regulation and immunosuppression (25,29).…”

Section: Peripheral Blood Mononuclear Cell Protein Expression Levels mentioning

confidence: 59%

Reduced Peripheral Blood Mononuclear Cell ROCK1 and ROCK2 Levels in Obstructive Sleep Apnea Syndrome

2018

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Abstract. Background Obstructive sleep apnea syndrome (OSAS) is one of the most frequent sleep disorders with a prevalence of 2-4% in the adult population, 3.1%-7.5% in men and 1.8%-5% in women (1-9). OSAS is characterized by repetitive episodes of apnea due to total compression of respiratory tract, intermittent hypoxia, reduced blood oxygen saturation and impaired sleep quality. It may cause difficulty sleeping, morning headache, daytime sleepiness, fatigue and reduced performance in daytime activities. Age, male gender and obesity have been listed among the risk factors of OSAS (1-3, 10). Moreover, OSAS has been associated with increased risk for arterial and pulmonary hypertension, cardiovascular and cerebrovascular disorders and metabolic syndrome (2,(11)(12)(13)(14).Although pathophysiological processes underlying OSAS have not been fully understood, inflammation, vascular endothelial dysfunction and altered body metabolism have been implicated (15,16). Rho-associated protein kinase (ROCK) enzyme is known to be involved in regulation of vascular functions and cardiovascular disease pathogenesis. ROCK activation has been shown to enhance endothelial permeability and induce angiogenic processes through regulation of endothelial gene expression (17). In several studies, ROCK enzyme activity has been shown to be altered in patients characterized with cardiorespiratory problems that might potentially lead to chronic hypoxia of the target tissue (e.g. brain, heart etc.) (18,19). In a single study, ROCK activity has been shown to be increased in OSAS in correlation with increased C-reactive protein (CRP) concentration and reduced flow-mediated dilatation in the brachial artery suggesting the presence of an interplay with ROCK and endothelial dysfunction (20).The present study was conducted to find out whether intermittent hypoxia induced by OSAS might alter ROCK1 and ROCK2 expression in the peripheral blood and thus levels of these proteins can be used to extrapolate the intensity of hypoxia induced by OSAS. Clinical and laboratory features that might potentially be associated with ROCK expression levels were also investigated. 319This article is freely accessible online.Correspondence to: Erdem Tüzün,

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“…Rho-kinase activity was assessed by measuring the levels of phosphorylated to total myosin-binding subunit (MBS) of myosin light-chain phosphatase, a direct downstream target of Rho-kinase, and by analysis of total Rho-kinase isoforms in circulating leukocytes from venous blood, as previously reported [4], [5], [6], [7], [8], [9]. Fasting venous blood was collected at room temperature in EDTA tubes with fasudil.…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

Data for increased Rho kinase activity in type 2 diabetic patients

et al. 2016

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The data presented in this article are related to the research article entitled “Enhanced Rho-Kinase Activity: Pathophysiological Relevance in Type 2 Diabetes” [1]. Rho-Kinase has attracted a great deal of interest as a novel therapeutic target in cardiovascular diseases. These data describe the observed relationship of Rho-Kinase activity with type 2 diabetic patients. Rho-Kinase activity is determined by immunoblotting of peripheral blood leukocytes with the Phospho-Thr853 in the myosin-binding subunit of myosin light-chain phosphatase. The level of IL-6 is measured using Enzyme-linked immunosorbent assay.

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Increased RhoA/Rho-Kinase Activity and Markers of Endothelial Dysfunction in Young Adult Subjects with Metabolic Syndrome

Abstract: Increased markers of cardiovascular risk are already present in young adults with metabolic syndrome but without type 2 diabetes or hypertension.

Cited by 23 publications

References 44 publications

BLT2 expression improves skin integrity and protects from alterations caused by hyperglycemia in type 2 diabetes

BLT2 expression improves skin integrity and protects from alterations caused by hyperglycemia in type 2 diabetes

Reduced Peripheral Blood Mononuclear Cell ROCK1 and ROCK2 Levels in Obstructive Sleep Apnea Syndrome

Data for increased Rho kinase activity in type 2 diabetic patients

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