11 research outputs found
Oxysterols and Retinal Microvascular Dysfunction as Early Risk Markers for Cardiovascular Disease in Normal, Ageing Individuals
Get PDFThe aim of the present paper is to assess the relationship between oxysterol levels and retinal microvascular function in individuals of various age groups, free of clinically evident diseases. Forty-two apparently healthy individuals were included in the present study (group 1: 19–30 years, group 2: 31–50 years, and group 3: 51–70 years). Retinal microvascular function was assessed using the dynamic retinal vessel analyzer (DVA, IMEDOS GmbH, Jena, Germany). Fasting plasma was obtained from all subjects and quantification of monohydroxy and dihydroxy oxysterols assessment was performed using LC-MS/MS following reverse phase chromatography. A Griess assay was used to evaluate the Nitric Oxide (NO) concentration in all individuals. The glutathione redox ratio was also analyzed by means of whole blood glutathione recycling assay. In all participants, the levels of 7-Ketocholesterol, 25-hydroxycholesterol and 7β-hydroxycholesterol correlated significantly and positively with the time to maximum arteriolar dilation. In addition, 25-hydroxycholesterol and 7β-hydroxycholesterol negatively correlated to the percentage of maximum arteriolar dilation. A negative correlation was observed for 27-hydroxycholesterol and 7β-hydroxycholesterol with microvascular arteriolar constriction. These results suggest that, with age, abnormal oxysterol levels correlate with early changes in microvascular bed function. This relationship could signal early risk for cardiovascular diseases (CVDs) in an ageing population
Datasets of whole cell and mitochondrial oxysterols derived from THP-1, SH-SY5Y and human peripheral blood mononuclear cells using targeted metabolomics
Get PDFThe raw datasets of oxysterol quantifications from whole cell and mitochondrial fractions of THP-1 monocytes and macrophages, neuronal-like SH-SH5Y cells and human peripheral blood mononuclear cells are presented. Oxysterols were quantified using a new liquid chromatography-mass spectrometry (LC-MS) and multiple reaction monitoring analysis published in the article “A quantitative LC-MS/MS method for analysis of mitochondrial-specific oxysterol metabolism” in Redox Biology [1]. This method showed improved extraction efficiency and recovery of mono and dihydroxycholesterols from cellular matrix. The datasets derived from the three cell lines are included in the appendix. These datasets provide new information about the oxysterol distribution in THP-1 monocytes and macrophages, SH-SY5Y cells and peripheral blood mononuclear cells. These datasets can be used as a guide for oxysterol distribution in the three cell lines for future studies, and can used for future method optimization, and for comparison of oxysterol recovery with other analytical techniques
The Use of Retinal Microvascular Function and Telomere Length in Age and Blood Pressure Prediction in Individuals with Low Cardiovascular Risk
Get PDFAgeing represents a major risk factor for many pathologies that limit human lifespan, including cardiovascular diseases. Biological ageing is a good biomarker to assess early individual risk for CVD. However, finding good measurements of biological ageing is an ongoing quest. This study aims to assess the use retinal microvascular function, separate or in combination with telomere length, as a predictor for age and systemic blood pressure in individuals with low cardiovascular risk. In all, 123 healthy participants with low cardiovascular risk were recruited and divided into three groups: group 1 (less than 30 years old), group 2 (31-50 years old) and group 3 (over 50 years old). Relative telomere length (RTL), parameters of retinal microvascular function, CVD circulatory markers and blood pressure (BP) were measured in all individuals. Symbolic regression- analysis was used to infer chronological age and systemic BP measurements using either RTL or a combination of RTL and parameters for retinal microvascular function. RTL decreased significantly with age ( = 0.010). There were also age-related differences between the study groups in retinal arterial time to maximum dilation ( = 0.005), maximum constriction ( = 0.007) and maximum constriction percentage ( = 0.010). In the youngest participants, the error between predicted versus actual values for the chronological age were smallest in the case of using both retinal vascular functions only ( = 0.039) or the combination of this parameter with RTL ( = 0.0045). Systolic BP was better predicted by RTL also only in younger individuals ( = 0.043). The assessment of retinal arterial vascular function is a better predictor than RTL for non-modifiable variables such as age, and only in younger individuals. In the same age group, RTL is better than microvascular function when inferring modifiable risk factors for CVDs. In older individuals, the accumulation of physiological and structural biological changes makes such predictions unreliable
MZe786, a hydrogen sulfide-releasing aspirin prevents preeclampsia in heme oxygenase-1 haplodeficient pregnancy under high soluble flt-1 environment
Get PDFPreeclampsia affects one in twelve of the 130 million pregnancies a year. The lack of an effective therapeutic to prevent or treat it is responsible for an annual global cost burden of 100 billion US dollars. Preeclampsia also affects these women later in life as it is a recognised risk factor for cardiovascular disease, stroke and vascular dementia. Our laboratory demonstrated that preeclampsia is associated with high soluble fms-like tyrosine kinase 1 (sFlt-1) and low heme oxygenase-1 (HO1/Hmox1) expression. Here we sought to determine the therapeutic value of a novel H 2S-releasing aspirin (MZe786) in HO-1 haploid deficient (Hmox1 +/−) pregnant mice in a high sFlt-1 environment. Pregnant Hmox1 +/− mice were injected with adenovirus encoding sFlt-1 or control virus at gestation day E11.5. Subsequently, Hmox1 +/− dams were treated daily with a number of treatment regimens until E17.5, when maternal and fetal outcomes were assessed. Here we show that HO-1 compromised mice in a high sFlt-1 environment during pregnancy exhibit severe preeclampsia signs and a reduction in antioxidant genes. MZe786 ameliorates preeclampsia by reducing hypertension and renal damage possibly by stimulating antioxidant genes. MZe786 also improved fetal outcome in comparison with aspirin alone and appears to be a better therapeutic agent at preventing preeclampsia than aspirin alone
Exploring mitochondrial hydrogen sulfide signalling for therapeutic interventions in vascular diseases
Get PDFHydrogen sulfide (H2S), a gaseous signalling molecule, is important in numerous physiological and pathophysiological processes. Despite its initial identification as an environmental toxin, H2S is now well described as an essential physiological molecule that is finely balanced to maintain cellular functions, especially in modulating mitochondrial activity. Mitochondria are responsible for the oxidation of H2S and its safe elimination while maintaining mitochondrial biogenesis. H2S oxidation in mitochondria generates various reactive sulfur species that could post-translationally modify proteins by sulfhydration. Sulfhydrated proteins participate in many regulatory activities either by direct interactions in the electron transport chain or indirect regulation by epigenetics. These investigations explain the importance of research of H2S as a therapeutic molecule beyond the traditional understanding as a protective role through its anti-inflammatory and antioxidant properties. This review focuses on highlighting the significant involvement of the H2S pathway in vascular diseases and current H2S donors for therapeutic use under development
Oxidative stress links periodontal inflammation and renal function
Get PDFAims: Patients with chronic kidney disease (CKD) are also susceptible to periodontitis. The causal link between periodontitis and CKD may be mediated via systemic inflammation/oxidative stress. Using structural equation modelling (SEM), this cross-sectional study aimed to explore the causal relationship between periodontal inflammation (PI) and renal function. Materials and methods: Baseline data on 770 patients with stage 3–5 (pre-dialysis) CKD from an ongoing cohort study were used. Detailed, bioclinical data on PI and renal function, as well as potential confounders and mediators of the relationship between the two, were collected. SEMs of increasing complexity were created to test the causal assumption that PI affects renal function and vice versa. Results: Structural equation modelling confirmed the assumption that PI and renal function are causally linked, mediated by systemic oxidative stress. The magnitude of this effect was such that a 10% increase in PI resulted in a 3.0% decrease in renal function and a 10% decrease in renal function resulted in a 25% increase in PI. Conclusions: Periodontal inflammation represents an occult source of oxidative stress in patients with CKD. Further clinical studies are needed to confirm whether periodontal therapy, as a non-pharmacological approach to reducing systemic inflammatory/oxidative stress burden, can improve outcomes in CKD
Healthy ageing and depletion of intracellular glutathione influences T cell membrane thioredoxin-1 levels and cytokine secretion
Get PDFBackground: During ageing an altered redox balance has been observed in both intracellular and extracellular compartments, primarily due to glutathione depletion and metabolic stress. Maintaining redox homeostasis is important for controlling proliferation and apoptosis in response to specific stimuli for a variety of cells. For T cells, the ability to generate specific response to antigen is dependent on the oxidation state of cell surface and cytoplasmic protein-thiols. Intracellular thiols are maintained in their reduced state by a network of redox regulating peptides, proteins and enzymes such as glutathione, thioredoxins and thioredoxin reductase. Here we have investigated whether any relationship exists between age and secreted or cell surface thioredoxin-1, intracellular glutathione concentration and T cell surface thioredoxin 1 (Trx-1) and how this is related to interleukin (IL)-2 production.Results: Healthy older adults have reduced lymphocyte surface expression and lower circulating plasma Trx-1 concentrations. Using buthionine sulfoximine to deplete intracellular glutathione in Jurkat T cells we show that cell surface Trx-1 is lowered, secretion of Trx-1 is decreased and the response to the lectin phytohaemagglutinin measured as IL-2 production is also affected. These effects are recapitulated by another glutathione depleting agent, diethylmaleate.Conclusion: Together these data suggest that a relationship exists between the intracellular redox compartment and Trx-1 proteins. Loss of lymphocyte surface Trx-1 may be a useful biomarker of healthy ageing. © 2013 Carilho Torrao et al.; licensee Chemistry Central Ltd
Circulating Oxysterols in Alzheimer’s disease: A Systematic Review and Meta-analysis
Get PDFDespite decades of research, the cause and series of events underlying the advancement of Alzheimer’s disease (AD) has not yet been established. Lipids and especially cholesterol levels have been proposed to be implicated in AD. Several studies have been undertaken and many ongoing in different directions looking at the importance of circulating cholesterols and oxidised cholesterols in Alzheimer’s disease with inconsistent methods and results. This meta-analysis aims to systematically analyse available data describing the involvement of oxidised cholesterols in Mild cognitive impairment (MCI) and Alzheimer’s disease (AD). We conducted a systematic literature search of 6 databases MEDLINE (PubMed), BIOSIS (Web of Science), EMBASE (Elsevier), PsycNET, Scopus and Cochrane library for studies measuring oxysterols (24-hydroxycholesterol (24OHC); 26-hydroxycholesterol (26OHC) and 7-oxycholesterols) in serum or plasma from MCI / AD patients compared to age and gender matched cognitively normal controls. Data was analysed using the inverse variance and standard mean difference with random effect analysis model at 95% confidence interval for association between oxysterols and MCI / AD in Review Manager (RevMan) software version 5.4.1. 175 studies between January 2000 and April 2022 were identified by 2 independent researchers out of which 14 met the inclusion criteria and were analysed with a total of 957 controls, 469 MCI cases and 509 AD cases. The standard mean differences between MCI / AD participants and controls did not show any difference in the oxysterol levels except for 26OHC level which were higher in AD but not statistically significant
