Role of Circulating Karyocytes in the Initiation and Progression of Atherosclerosis

Chon, Helena; Verhaar, Marianne C.; Koomans, Hein A.; Joles, Jaap A.; Braam, Branko

doi:10.1161/01.hyp.0000210554.61293.90

Cited by 18 publications

(16 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, functionally, the net response observed from these heterogeneous cell populations is more representative of an intact system as opposed to individual populations of cells. Furthermore, it is important to note that these findings are from primary human cells and not from an immortalized cell line, providing a foundation for future patient studies to examine cellular mechanisms and also potentially to elucidate biomarkers for health and disease (8,32). Interestingly, the observed variability in our gene expression data is similar to most physiological data obtained in humans (2).…”

Section: Discussionsupporting

confidence: 51%

Norepinephrine increases NADPH oxidase-derived superoxide in human peripheral blood mononuclear cells via α-adrenergic receptors

Deo

Jenkins

Padilla

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Deo SH, Jenkins NT, Padilla J, Parrish AR, Fadel PJ. Norepinephrine increases NADPH oxidase-derived superoxide in human peripheral blood mononuclear cells via ␣-adrenergic receptors. Am J Physiol Regul Integr Comp Physiol 305: R1124 -R1132, 2013. First published September 25, 2013 doi:10.1152/ajpregu.00347.2013.-Many diseases associated with sympathoexcitation also exhibit elevated reactive oxygen species (ROS). A recent animal study indicated that exogenous administration of the sympathetic neurotransmitter norepinephrine (NE) increased systemic ROS via circulating leukocytes. The mechanisms contributing to this effect of NE and whether these findings can be translated to humans is unknown. Thus we tested the hypothesis that NE increases superoxide production in human peripheral blood mononuclear cells (PBMCs) via NADPH oxidase. Primary human PBMCs were freshly isolated from healthy young men and placed in culture. After NE (50 pg/ml, 50 ng/ml, and 50 g/ml concentrations) or control treatments, NADPH oxidase mRNA expression (gp91 phox , p22 phox , and p67 phox ) was assessed using realtime RT-PCR, and intracellular superoxide production was measured using dihydroethidium fluorescence. PBMCs were also treated with selective adrenergic agonists-antagonists to determine the receptor population involved. In addition, CD14ϩ monocyte-endothelial cell adhesion was determined using a fluorescent-based assay. NE significantly increased NADPH oxidase gene expression and intracellular superoxide production in a time-dependent manner (superoxide: 0.9 Ϯ 0.2 fold, 6 h vs. 3.0 Ϯ 0.3 fold, 36 h; NE, 50 g/ml; P Ͻ 0.05). The sustained increase in NE-induced superoxide production was primarily mediated via ␣-adrenergic receptors, preferentially ␣ 2-receptors. The NADPH oxidase blocker diphenylene iodonium and protein kinase C inhibitor Staurosporine significantly attenuated NE-induced increases in superoxide production. Importantly, NE treatment increased CD14ϩ monocyte-endothelial cell adhesion. These findings indicate for the first time that NE increases superoxide production in freshly isolated primary human PBMCs via NADPH oxidase through ␣-adrenergic receptors, an effect facilitating monocyte adhesion to the endothelium. sympathetic nerve activity; reactive oxygen species; oxidative stress CHRONICALLY ELEVATED SYMPATHETIC NERVE ACTIVITY is a hallmark characteristic of several cardiovascular diseases (14,17,29). Recently, many of these diseases have also been shown to exhibit elevated systemic oxidative stress (9,19,38). However, it is unclear whether elevated oxidative stress causes sympathoexcitation or vice versa.Numerous studies performed in animals have convincingly shown that an increase in central superoxide levels induces activation of key brain areas, such as the rostral ventrolateral medulla, to cause sympathoexcitation (4,33,44,53,54). In contrast, to our knowledge, little consideration has been given to the potential ability of the sympathetic neurotransmitter norepinephrine (NE) to increase oxidative stress. In...

show abstract

Section: Discussionsupporting

confidence: 51%

Norepinephrine increases NADPH oxidase-derived superoxide in human peripheral blood mononuclear cells via α-adrenergic receptors

Deo

Jenkins

Padilla

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…Yet, the increased WBC count in hyperuricemic patients with MS may be a possible explanation. WBC, as one subtype of immune cells, could interact with the endothelial cells by producing and releasing reactive oxygen species and cytokines, which could influence gene and protein expression, intracellular signaling, and vasodilation in response to vascular-active substances [31]. Simultaneously, neutrophils and monocytes, as parts of WBC, were independently related with UA [32].…”

Section: Discussionmentioning

confidence: 99%

Relationship between Uric Acid and Endothelial Function in Hypertensive Patients with Metabolic Syndrome

Huang¹,

Cai²,

Zheng³

et al. 2016

J Clin Exp Cardiolog

View full text Add to dashboard Cite

Aim: To investigate the association between uric acid (UA) and endothelial function in Chinese hypertensive patients with Metabolic Syndrome (MS).Methods: 615 hypertensive patients were enrolled, all hypertensives were divided into two groups: hypertensives with MS (MS group, n=239) and hypertensives without MS (NMS group, n=376). 87 age-and sex-matched normotensives served as controls (NC group). Flow-mediated (endothelium-dependent) dilatations (FMD), nitroglycerin-induced (endothelium-independent) dilatation (EID) in the brachial artery were assessed by highresolution ultrasonography. UA was detected by urease indophenol. .58)%, p<0.001) among groups. After stratification of gender, lower FMD was only seen in male hypertensives with MS accompanied by hyperuricemia <60 years old ((9.98 ± 5.78)% vs (7.12 ± 4.49)%, p<0.05); Pearson correlation analysis showed that the FMD was negatively correlated with UA (r=-0.314, p<0.01); Finally, logistic regression analysis showed that a 50 µmol/L increase in UA levels carried a 41.1% higher risk for endothelial dysfunction in this cohort. Conclusions: A higher UA level is related to poorer endothelial function in hypertensives with MS. Increased UA can be used as an alternative indicator for monitoring endothelial function and preventing vascular damage in male hypertensives with MS aged less than 60 years old.Keywords: Uric acid; Endothelial dysfunction; Hypertension; Metabolic syndrome InstructionRecently, several studies have indicated that uric acid (UA), the circulating end-metabolite of purine nucleotides of mankind, is associated with subsequent cardiovascular diseases [1,2]. However, it remains controversial whether UA is a relevant and independent risk factor for cardiovascular disease and the mechanisms by which UA results in target organ injury are still unknown. Increasing data suggest that UA is associated with endothelial dysfunction [3,4], which is characteristic of patients with essential hypertension [5]. It is well recognized that endothelial dysfunction is an early stage in atherogenesis and associates with poor cerebro-cardiovascular outcomes [6]. It has been shown that UA disturbs endothelial function by disrupting nitric oxide (NO) synthesis, inhibiting NO bioavailability and activating the renin-angiotensin system.Metabolic syndrome (MS) is believed to be a clustering of abnormalities of several cardiovascular risk factors in an individual including abdominal obesity, hypertension, and dyslipidemia, including low HDL-C, high LDL-C and hyperglycemia. MS is often associated with elevated UA levels [7] and endothelial dysfunction [8,9]. The prevalence of MS has been increasing in recent years in China. A recent epidemiological study showed that the prevalence of MS among Chinese men and women aged 35 to 64 years old was 9.8% and 17.8%, respectively [10]. As is known to all, MS is quite common in patients with primary hypertension and carries much higher risk of cardiovascular events. It was reported that nearly 90% of Chinese hypertensives were ...

show abstract

“…PBMC synthesize inflammatory proteins and reactive oxygen species that can cause damage and dysfunction to arteries and other tissues. It has been postulated that a proinflammatory/-oxidant gene expression profile in PBMC may contribute to increased risk of CVD (4). Consistent with this, mRNA expression of some inflammatory genes is altered in PBMC obtained from untreated patients with essential hypertension, an effect that is absent in patients undergoing successful antihypertensive therapy (3).…”

mentioning

confidence: 85%

Increased proinflammatory and oxidant gene expression in circulating mononuclear cells in older adults: amelioration by habitual exercise

Gano

Donato

Pierce

et al. 2011

Physiological Genomics

View full text Add to dashboard Cite

We tested the hypothesis that peripheral blood mononuclear cells (PBMC) of older adults demonstrate a proinflammatory/-oxidative gene expression profile that can be improved by regular aerobic exercise. PBMC were isolated from young (n ϭ 25, 18 -33 yr) and middle-aged/older (n ϭ 40, 50 -76 yr) healthy adults. The older adults had greater mRNA expression (real-time RT-PCR) of the proinflammatory/-oxidant transcription factor nuclear factor-B (1.58-fold, P Ͻ 0.05) and receptor for advanced glycation end products (1.12-fold, P Ͻ 0.05), the proinflammatory cytokines tumor necrosis factor-␣ (1.90-fold, P Ͻ 0.05) and monocyte chemoattractant protein-1 (1.47-fold, P Ͻ 0.05), and the oxidant-producing enzymes nicotinamide adenine dinucleotide phosphate-oxidase (0.91-fold, P Ͻ 0.05) and inducible nitric oxide synthase (2.60-fold, P Ͻ 0.05). In 11 subjects (58 -70 yr), maximal oxygen consumption (ϩ11%) and exercise time (ϩ19%) were increased (both P Ͻ 0.001), and expression of the above proinflammatory/-oxidative genes was or tended to be decreased in PBMC after vs. before 2 mo of aerobic exercise (brisk walking ϳ6 days/wk, 50 min/day, 70% of maximal heart rate). Expression of interleukin-6 was not different with age or exercise intervention. Age group-and exercise intervention-related differences in gene expression were independent of other factors. PBMC of healthy older adults demonstrate increased expression of several genes associated with inflammation and oxidative stress, which is largely ameliorated by habitual aerobic exercise. This proinflammatory/-oxidative gene signature may represent a therapeutic target for lifestyle and pharmacological prevention and treatment strategies. aging; oxidative stress; inflammation; cytokines; immune cells AGE IS THE MAJOR RISK FACTOR for cardiovascular diseases (CVD), largely as the result of vascular dysfunction (18). Chronic low-grade inflammation and oxidative stress are believed to play important roles in the development of vascular disorders with age (1, 29, 31). Plasma markers of inflammation and oxidative stress often are elevated in older adults (9,11,13). Proinflammatory changes to the intimal layer of arteries with aging have been reported on autopsy (34). Moreover, we recently found increased expression of the redox-sensitive proinflammatory nuclear transcription factor nuclear factor B (NF-B), the proinflammatory cytokines tumor necrosis factor-␣ (TNF-␣), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1), and the oxidant enzyme nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase in vascular endothelial cells obtained from older compared with young adults (9, 10). The proinflammatory/redox-sensitive proteins receptor for advanced glycation end products (RAGE) and inducible nitric oxide synthase (iNOS) also have been found to increase with age (2, 15).Although evidence is accumulating for inflammation and oxidative stress in plasma and vascular cells/tissues with advancing age in humans, relatively little is known about the possibility of such...

show abstract

Role of Circulating Karyocytes in the Initiation and Progression of Atherosclerosis

Abstract: Abstract-Cardiovascular

Cited by 18 publications

References 96 publications

Norepinephrine increases NADPH oxidase-derived superoxide in human peripheral blood mononuclear cells via α-adrenergic receptors

Norepinephrine increases NADPH oxidase-derived superoxide in human peripheral blood mononuclear cells via α-adrenergic receptors

Relationship between Uric Acid and Endothelial Function in Hypertensive Patients with Metabolic Syndrome

Increased proinflammatory and oxidant gene expression in circulating mononuclear cells in older adults: amelioration by habitual exercise

Contact Info

Product

Resources

About