Vascular Biology of the Isoprostanes

Cracowski, Jean‐Luc; Devillier, Philippe; Stanke‐Labesque, Françoise; Bessard, Germain

doi:10.1159/000051036

Cited by 101 publications

(70 citation statements)

References 87 publications

(144 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[15][16][17][18] Although an increase in the 8-iso-PG level is indirect evidence of endothelial dysfunction, 8-iso-PG is a specific marker of oxidative injury in vasculitis. [19][20][21][22] Our study demonstrated that OS activation plays an important role in the pathological process of the acute phase of KD. In addition, 8-iso-PG is also a reliable marker of OS in the acute phase of KD and may be a sensitive marker of the effects of IVIG therapy.…”

Section: Discussionmentioning

confidence: 52%

IVIG Reduced Vascular Oxidative Stress in Patients With Kawasaki Disease

Takatsuki

Ito

Takeuchi

et al. 2009

Circ J

View full text Add to dashboard Cite

xidative stress (OS) plays an important role in vascular diseases. Endothelial dysfunction activates the pathway that leads to elevated OS. 1 In particular, oxidative damage occurs when the delicate balance between pro-and antioxidant molecules, which act against free radical injury, is upset. This balance may be destroyed by certain risk factors; for example, atherosclerosis, hypertension, hyperlipidemia, diabetes and cigarette smoking. [2][3][4][5][6] The 8-isoprostaglandin F2α (8-iso-PG) is a nonenzymatic oxidation product of arachidonic acid and is widely recognized as a reliable marker of lipid peroxidation both in vitro and in vivo. 3,4,7 Enhanced endothelial dysfunction, as reflected by increased 8-iso-PG excretion, has been reported previously. [3][4][5] Kawasaki disease (KD) is a systemic vasculitis and an acute febrile illness (FI) in children. Recent studies have shown activation of the immune system is involved and multiple factors are likely to cause the pathologic changes seen in KD. [8][9][10][11] How OS contributes to the acute phase of KD is as yet unknown.In the present study, we investigated OS in the acute phase of KD by measuring urinary 8-iso-PG and evaluated its correlation to the efficacy of intravenous immunoglobulin (IVIG) treatment. Methods PatientsAll subjects of this study were typical KD patients admitted to Toho University Hospital between March 2002 and September 2004. They were given IVIG (1-2 g/kg) therapy in the acute phase: 62 patients (37 boys, 25 girls, median age: 4 years, range: 2 months to 11 years) were enrolled. None of the patients had other disorders, such as infection, collagen disease or congenital heart disease. We also studied 20 healthy children (HC, median age: 4 years, range: 1-11 years) and 20 patients with an acute FI such as viral pharyngitis and tonsillitis (median age: 5 years, range: 1-10 years). Informed consent was given by the parents of the patients participating in the study. Biochemical MeasurementsUrinary 8-iso-PG was measured by enzyme immunoassay and the concentration was corrected by urinary creatinine concentration. The samples were obtained before and after IVIG administration. In the HC and FI groups inflammatory markers such as C-reactive protein (CRP), white blood cell (WBC) count, neutrophil count, albumin level and erythrocyte sedimentation rate (ESR) were measured at the same time. Echocardiography was performed in the patients in the acute phase of KD. Statistical AnalysisDifferences between continuous variables were evaluated by t-test. The data for each group were analyzed using ANOVA. The relationship between 2 different parameters was obtained by simple regression analysis. A P-value <0.05 was considered statistically significant. (Received August 29, 2007; revised manuscript received February 2, 2009; accepted February 18, 2009; released online May 13, 2009) Pediatrics, Toho University Omori Medical Center, Tokyo, Japan Mailing address: Shinchi Takatsuki, MD, Pediatrics, Toho University Omori Medical Center, 6-11-1 Omorinishi, O...

show abstract

Section: Discussionmentioning

confidence: 52%

IVIG Reduced Vascular Oxidative Stress in Patients With Kawasaki Disease

Takatsuki

Ito

Takeuchi

et al. 2009

Circ J

View full text Add to dashboard Cite

show abstract

“…Several cardiovascular pathologies are characterized by elevated isoprostane formation and excretion (Cracowski et al, 2001;Cracowski and Durand, 2006;Schwedhelm et al, 2007). Moreover, isoprostanes are involved in the pathophysiology of CVD by activating the TP receptor (Galano et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Pathophysiology of isoprostanes in the cardiovascular system: implications of isoprostane‐mediated thromboxane A₂ receptor activation

Bauer

Ripperger

Frantz

et al. 2014

British J Pharmacology

132

108

View full text Add to dashboard Cite

Isoprostanes are free radical-catalysed PG-like products of unsaturated fatty acids, such as arachidonic acid, which are widely recognized as reliable markers of systemic lipid peroxidation and oxidative stress in vivo. Moreover, activation of enzymes, such as COX-2, may contribute to isoprostane formation. Indeed, formation of isoprostanes is considerably increased in various diseases which have been linked to oxidative stress, such as cardiovascular disease (CVD), and may predict the atherosclerotic burden and the risk of cardiovascular complications in the latter patients. In addition, several isoprostanes may directly contribute to the functional consequences of oxidant stress via activation of the TxA2 prostanoid receptor (TP), for example, by affecting endothelial cell function and regeneration, vascular tone, haemostasis and ischaemia/reperfusion injury. In this context, experimental and clinical data suggest that selected isoprostanes may represent important alternative activators of the TP receptor when endogenous TxA2 levels are low, for example, in aspirin-treated individuals with CVD. In this review, we will summarize the current understanding of isoprostane formation, biochemistry and (patho) physiology in the cardiovascular context. IntroductionOxidative stress in biological systems is defined as an imbalance between the generation of reactive oxygen species (ROS) and antioxidant defence mechanisms (Dalle-Donne et al., 2006;Giustarini et al., 2009). In contrast to the physiological condition, during which ROS are only present at moderate levels and play an important role as messengers in redox signalling, in pathological conditions, when the physiological redox state of cells is disturbed, ROS can severely affect cellular signalling and function. Indeed, ROS which are not neutralized or scavenged by antioxidant molecules, such as GSH or superoxide dismutase, may react with nucleic acids and proteins and thereby alter the biochemical and physical properties of these important cellular components. Moreover, exposure of lipids to free radicals induces a non-enzymatic reaction cascade resulting in an increased formation of bioactive molecules named isoprostanes. Consequently, systemic isoprostane formation is significantly increased in a variety of pathological processes associated with oxidative stress, for example, cancer as well as, cardiovascular, metabolic and neurodegenerative diseases, and isoprostanes are increasingly recognized not only as markers of oxidative stress but also as mediators of disease progression (Praticò et al., 1997;Reilly et al., 1998;Davì et al., 1999;Minuz et al., 2002;Vassalle et al., 2003;Schwedhelm et al., 2004, Xia et al., 2005Montuschi et al., 2007;Schwedhelm et al., 2010; Barocas et al., 2011;Davies and Roberts, 2011; KhademAnsari et al., 2011;Montine et al., 2011;Sbardella et al., 2013). Isoprostanes are PG-like compounds derived from lipid peroxidation of esterified unsaturated fatty acids, for example, arachidonic acid, which are primarily generated in a free rad...

show abstract

“…Quantification of F 2 -IsoPs has been shown to be one of the most reliable markers to assess oxidant stress status and lipid peroxidation in vivo (5)(6)(7). In addition, F 2 -IsoPs have been shown to exert potent vasoconstrictive activities in the vasculature (8,9), suggesting a pathogenic role for these compounds in diseases such as atherosclerosis (10,11).…”

mentioning

confidence: 99%

Formation of F-ring Isoprostane-like Compounds (F3-Isoprostanes) in Vivo from Eicosapentaenoic Acid

Gao¹,

Yin²,

Milne³

et al. 2006

Journal of Biological Chemistry

116

View full text Add to dashboard Cite

Eicosapentaenoic acid (EPA, C20:5, -3) is the most abundant polyunsaturated fatty acid (PUFA) in fish oil. Recent studies suggest that the beneficial effects of fish oil are due, in part, to the generation of various free radical-generated non-enzymatic bioactive oxidation products from -3 PUFAs, although the specific molecular species responsible for these effects have not been identified. Our research group has previously reported that pro-inflammatory prostaglandin F 2 -like compounds, termed F 2 -isoprostanes (IsoPs), are produced in vivo by the free radical-catalyzed peroxidation of arachidonic acid and represent one of the major products resulting from the oxidation of this PUFA. Based on these observations, we questioned whether F 2 -IsoP-like compounds (F 3 -IsoPs) are formed from the oxidation of EPA in vivo. Oxidation of EPA in vitro yielded a series of compounds that were structurally established to be F 3 -IsoPs using a number of chemical and mass spectrometric approaches. The amounts formed were extremely large (up to 8.7 ؉ 1.0 g/mg EPA) and greater than levels of F 2 -IsoPs generated from arachidonic acid. We then examined the formation of F 3 -IsoPs in vivo in mice. Levels of F 3 -IsoPs in tissues such as heart are virtually undetectable at baseline, but supplementation of animals with EPA markedly increases quantities up to 27.4 ؉ 5.6 ng/g of heart. Interestingly, EPA supplementation also markedly reduced levels of pro-inflammatory arachidonate-derived F 2 -IsoPs by up to 64% ( p < 0.05). Our studies provide the first evidence that identify F 3 -IsoPs as novel oxidation products of EPA that are generated in vivo. Further understanding of the biological consequences of F 3 -IsoP formation may provide valuable insights into the cardioprotective mechanism of EPA.

show abstract

Vascular Biology of the Isoprostanes

Cited by 101 publications

References 87 publications

IVIG Reduced Vascular Oxidative Stress in Patients With Kawasaki Disease

IVIG Reduced Vascular Oxidative Stress in Patients With Kawasaki Disease

Pathophysiology of isoprostanes in the cardiovascular system: implications of isoprostane‐mediated thromboxane A₂ receptor activation

Formation of F-ring Isoprostane-like Compounds (F3-Isoprostanes) in Vivo from Eicosapentaenoic Acid

Contact Info

Product

Resources

About

Vascular Biology of the Isoprostanes

Cited by 101 publications

References 87 publications

IVIG Reduced Vascular Oxidative Stress in Patients With Kawasaki Disease

IVIG Reduced Vascular Oxidative Stress in Patients With Kawasaki Disease

Pathophysiology of isoprostanes in the cardiovascular system: implications of isoprostane‐mediated thromboxane A2 receptor activation

Formation of F-ring Isoprostane-like Compounds (F3-Isoprostanes) in Vivo from Eicosapentaenoic Acid

Contact Info

Product

Resources

About

Pathophysiology of isoprostanes in the cardiovascular system: implications of isoprostane‐mediated thromboxane A₂ receptor activation