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Vascular Inflammation and Oxidative Stress: Major Triggers for Cardiovascular Disease.

ABSTRACT: Cardiovascular disease is a leading cause of death and reduced quality of life, proven by the latest data of the Global Burden of Disease Study, and is only gaining in prevalence worldwide. Clinical trials have identified chronic inflammatory disorders as cardiovascular risks, and recent research has revealed a contribution by various inflammatory cells to vascular oxidative stress. Atherosclerosis and cardiovascular disease are closely associated with inflammation, probably due to the close interaction of inflammation with oxidative stress. Classical therapies for inflammatory disorders have demonstrated protective effects in various models of cardiovascular disease; especially established drugs with pleiotropic immunomodulatory properties have proven beneficial cardiovascular effects; normalization of oxidative stress seems to be a common feature of these therapies. The close link between inflammation and redox balance was also supported by reports on aggravated inflammatory phenotype in the absence of antioxidant defense proteins (e.g., superoxide dismutases, heme oxygenase-1, and glutathione peroxidases) or overexpression of reactive oxygen species producing enzymes (e.g., NADPH oxidases). The value of immunomodulation for the treatment of cardiovascular disease was recently supported by large-scale clinical trials demonstrating reduced cardiovascular mortality in patients with established atherosclerotic disease when treated by highly specific anti-inflammatory therapies (e.g., using monoclonal antibodies against cytokines). Modern antidiabetic cardiovascular drugs (e.g., SGLT2 inhibitors, DPP-4 inhibitors, and GLP-1 analogs) seem to share these immunomodulatory properties and display potent antioxidant effects, all of which may explain their successful lowering of cardiovascular risk.

SUBMITTER: Steven S

PROVIDER: S-EPMC6612399 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Vascular Inflammation and Oxidative Stress: Major Triggers for Cardiovascular Disease.

Steven Sebastian S Frenis Katie K Oelze Matthias M Kalinovic Sanela S Kuntic Marin M Bayo Jimenez Maria Teresa MT Vujacic-Mirski Ksenija K Helmstädter Johanna J Kröller-Schön Swenja S Münzel Thomas T Daiber Andreas A

Oxidative medicine and cellular longevity 20190623

Cardiovascular disease is a leading cause of death and reduced quality of life, proven by the latest data of the Global Burden of Disease Study, and is only gaining in prevalence worldwide. Clinical trials have identified chronic inflammatory disorders as cardiovascular risks, and recent research has revealed a contribution by various inflammatory cells to vascular oxidative stress. Atherosclerosis and cardiovascular disease are closely associated with inflammation, probably due to the close int ...[more]

PMID: 31341533

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Project description:Background: Increased arterial stiffness and vascular endothelial dysfunction are important nontraditional cardiovascular risk factors evident in patients with CKD. Vascular oxidative stress and inflammation may contribute to vascular dysfunction in CKD, but direct evidence is lacking.Methods: We assessed carotid-femoral pulse-wave velocity (arterial stiffness) and brachial artery flow-mediated dilation (vascular endothelial function) in participants with moderate-to-severe CKD (eGFR 15-59 ml/min per 1.73 m2) and in healthy controls. Change in brachial artery flow-mediated dilation after an acute infusion of ascorbic acid to inhibit vascular oxidative stress (versus saline) was also measured. Protein expression of vascular endothelial cells collected from a peripheral vein and ELISAs to assess circulating markers were also performed.Results: A total of 64 participants with CKD (mean±SD, 65±8 years) and 17 healthy controls (60±5 years) were included. Carotid-femoral pulse-wave velocity was greater in participants with CKD compared with healthy controls (1071±336 versus 732±128 cm/s; P<0.001). Brachial artery flow-mediated dilation was lower in participants with CKD compared with healthy controls (3.5%±2.8% versus 5.5%±3.2%; P=0.02). Circulating inflammation markers (C-reactive protein and IL-6) were elevated in the CKD group (P?0.02). Endothelial cell protein expression of NADPH (intensity versus human umbilical vein endothelial cell control, 1.48±0.28 versus 1.25±0.31; P=0.05) was greater in participants with CKD. However, ascorbic acid significantly improved brachial artery flow-mediated dilation in control participants (saline, 5.5±3.2; ascorbic acid, 6.8±3.6); as compared with participants with CKD (saline, 3.5±2.8; ascorbic acid, 3.6±3.2) (group×condition interaction P=0.04), suggesting vascular oxidative stress could not be overcome with ascorbic acid in participants with CKD.Conclusions: Vascular oxidative stress is present in CKD, which cannot be overcome with acute infusion of ascorbic acid.

Project description:BACKGROUND AND OBJECTIVES:Both increased arterial stiffness and vascular endothelial dysfunction are evident in patients with autosomal dominant polycystic kidney disease, even early in the course of the disease when kidney function in preserved. Vascular dysfunction in autosomal dominant polycystic kidney disease is thought to be related to vascular oxidative stress and inflammation, but direct evidence is lacking. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:We assessed carotid-femoral pulse-wave velocity (arterial stiffness) and brachial artery flow-mediated dilation (vascular endothelial function) in participants with early-stage autosomal dominant polycystic kidney disease (eGFR?60 ml/min per 1.73 m2) and a history of controlled hypertension and in healthy controls. Brachial artery flow-mediated dilation was also assessed after infusion of ascorbic acid to inhibit vascular oxidative stress compared with saline. Vascular endothelial cells were collected from a peripheral vein to measure expression of proteins, and circulating markers were also assessed by ELISA or liquid chromatography-tandem mass spectrometry. RESULTS:In total, 61 participants with autosomal dominant polycystic kidney disease (34±9 years old [mean±SD]) and 19 healthy controls (30±5 years old) were studied. Carotid-femoral pulse-wave velocity was higher in participants with autosomal dominant polycystic kidney disease compared with healthy controls (650±131 versus 562±81 cm/s; P=0.007). Brachial artery flow-mediated dilation was 8.2%±5.8% in participants with autosomal dominant polycystic kidney disease and 10.8%±4.7% in controls (P=0.08). Among participants with autosomal dominant polycystic kidney disease, flow-mediated dilation increased from 7.7%±4.5% to 9.4%±5.2% with ascorbic acid, a difference of 1.72 (95% confidence interval, 0.80 to 2.63), whereas in control participants, flow-mediated dilation decreased nonsignificantly from 10.8%±4.7% to 10.6%±5.4%, a difference of -0.20 (95% confidence interval, -1.24 to 0.84; P interaction =0.02). Endothelial cell protein expression of NF-?B was greater in participants with autosomal dominant polycystic kidney disease (0.48±0.12 versus 0.41±0.10 [intensity versus human umbilical vein endothelial cell control]; P=0.03). However, circulating oxidative stress markers and bioactive lipid mediators did not significantly differ according to the autosomal dominant polycystic kidney disease diagnosis. CONCLUSIONS:These results provide support for the hypothesis that vascular oxidative stress and inflammation develop with autosomal dominant polycystic kidney disease. PODCAST:This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_09_18_CJASNPodcast_18_10_.mp3.

Project description:Increased inflammation and oxidative stress have been shown in Major Depressive Disorder (MDD), although there is significant heterogeneity across studies. Whether markers of inflammation and oxidative stress are associated with antidepressant treatment response in MDD is currently unclear. The goals of the present study are to investigate markers of inflammation and oxidative stress in unmedicated MDD subjects and controls and test the relationship between these markers and antidepressant response in MDD subjects.Interleukin (IL)-6, tumor necrosis factor (TNF)-?, C-reactive protein, F2-isoprostanes, 8-OH 2-deoxyguanosine (8-OHdG), glutathione peroxidase, glutathione, and vitamin C were quantified in blood samples from 50 unmedicated MDD subjects and 55 healthy controls. Depression symptom severity was rated with the 17-item Hamilton Depression Rating Scale (HDRS). All subjects were somatically healthy and free from medications that could interfere with inflammation and oxidative stress markers. A subgroup of 22 MDD subjects underwent open-label selective serotonin reuptake inhibitor (SSRI) antidepressant treatment for eight weeks, after which blood sampling and the HDRS were repeated. Antidepressant treatment "response" was defined as ?50% decrease in HDRS ratings over 8 weeks of treatment.After controlling for the effects of age, sex, body mass index and smoking, MDD subjects had significantly higher levels of IL-6 (p<0.001), TNF-? (p<0.001), 8-OHdG (p=0.018), and F2-isoprostanes (p=0.012). Compared to Responders, Non-responders to SSRI antidepressant treatment had higher levels of F2-isoprostanes at baseline (p=0.006), and after eight weeks of treatment (p=0.031). Non-responders showed a significant increase in 8-OHdG over the course of treatment (p=0.021), whereas Responders showed a significant decrease in IL-6 over the course of treatment (p=0.019).Our results are in line with previous reports of increased levels of markers of inflammation and oxidative stress in MDD. Moreover, poorer antidepressant treatment response was related to higher baseline levels of the major oxidative stress marker, F2-isoprostanes, in vivo. Further, antidepressant response was associated with changes in oxidative (8-OHdG) and inflammatory (IL-6) markers.

Dataset Information

Vascular Inflammation and Oxidative Stress: Major Triggers for Cardiovascular Disease.

Publications

Vascular Inflammation and Oxidative Stress: Major Triggers for Cardiovascular Disease.

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