Acrolein, IL-6 and CRP as markers of silent brain infarction

Yoshida, Madoka; Tomitori, Hideyuki; Machi, Yoshiki; Katagiri, Daisuke; Ueda, Shiro; Horiguchi, Kentaro; Kobayashi, Eiichi; Saeki, Naokatsu; Nishimura, Kazuhiro; Ishii, Itsuko; Kashiwagi, Keiko; Igarashi, Kazuei

doi:10.1016/j.atherosclerosis.2008.07.022

Cited by 59 publications

(39 citation statements)

References 29 publications

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“…The same authors also demonstrated that the measurement of protein-conjugated acrolein (PC-ACR), together other indexes, can be a useful biomarker of small infarction and that ACR prevalently originates from spermine metabolism rather than from PUFAs peroxidation [76,77]. The levels of PC-ACR were significantly higher in subjects with silent brain infarction than in normal subjects [78]. Hence, according to these authors, the induction of brain infarction is well correlated with the increase in PC-ACR at the locus of infarction and in plasma, and ACR is more strongly involved than reactive oxygen species (ROS) in cell damage.…”

Section: Ex Vivo-in Vivo Studiesmentioning

confidence: 87%

Protein modification by acrolein: Relevance to pathological conditions and inhibition by aldehyde sequestering agents

Aldini

Orioli

Carini

2011

Molecular Nutrition Food Res

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Acrolein (ACR) is a toxic and highly reactive α,β-unsaturated aldehyde widely distributed in the environment as a common pollutant and generated endogenously mainly by lipoxidation reactions. Its biological effects are due to its ability to react with the nucleophilic sites of proteins, to form covalently modified biomolecules which are thought to be involved as pathogenic factors in the onset and progression of many pathological conditions such as cardiovascular and neurodegenerative diseases. Functional impairment of structural proteins and enzymes by covalent modification (crosslinking) and triggering of key cell signalling systems are now well-recognized signs of cell and tissue damage induced by reactive carbonyl species (RCS). In this review, we mainly focus on the in vitro and in vivo evidence demonstrating the ability of ACR to covalently modify protein structures, in order to gain a deeper insight into the dysregulation of cellular and metabolic pathways caused by such modifications. In addition, by considering RCS and RCS-modified proteins as drug targets, this survey will provide an overview on the newly developed molecules specifically tested for direct or indirect ACR scavenging, and the more significant studies performed in the last years attesting the efficacy of compounds already recognized as promising aldehyde-sequestering agents.

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Section: Ex Vivo-in Vivo Studiesmentioning

confidence: 87%

Protein modification by acrolein: Relevance to pathological conditions and inhibition by aldehyde sequestering agents

Aldini

Orioli

Carini

2011

Molecular Nutrition Food Res

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“…52 Data concerning IL-6 are more consistent because an independent association between IL-6 and either WMH or silent brain infarcts was shown by the majority of population and hospital-based studies. 51,60,67,69 Nevertheless, no association with the progression of MRI SVD markers was found for IL-6 in the 3C-Dijon study. 60 Only one study reported an association between IL-6, IL-18, and MB.…”

Section: 61mentioning

confidence: 89%

Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review

Poggesi

Pasi

Pescini

et al. 2015

J Cereb Blood Flow Metab

214

183

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The term cerebral small vessel disease (SVD) refers to a group of pathologic processes with various etiologies that affect small arteries, arterioles, venules, and capillaries of the brain. Magnetic resonance imaging (MRI) correlates of SVD are lacunes, recent small subcortical infarcts, white-matter hyperintensities, enlarged perivascular spaces, microbleeds, and brain atrophy. Endothelial dysfunction is thought to have a role in the mechanisms leading to SVD-related brain changes, and the study of endothelial dysfunction has been proposed as an important step for a better comprehension of cerebral SVD. Among available methods to assess endothelial function in vivo, measurement of molecules of endothelial origin in peripheral blood is currently receiving selective attention. These molecules include products of endothelial cells that change when the endothelium is activated, as well as molecules that reflect endothelial damage and repair. This review examines the main molecular factors involved in both endothelial function and dysfunction, and the evidence linking endothelial dysfunction with cerebral SVD, and gives an overview of clinical studies that have investigated the possible association between endothelial circulating biomarkers and SVD-related brain changes. KeywordsCerebral small vessel disease, endothelium, inflammation, lacunar infarcts, white-mater hyperintensities The term cerebral small vessel disease (SVD) refers to a group of pathologic processes with various etiologies that affect the small arteries, arterioles, venules, and capillaries of the brain.1 Age/hypertension-related SVDs and cerebral amyloid angiopathy are the most common sporadic forms of SVD. Among a few genetic forms of SVD, CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), caused by NOTCH3 gene mutations, is the most frequent one. It is a systemic arteriopathy although the clinical symptoms are those caused by brain dysfunction. The effects of both sporadic and inherited SVD on the brain parenchyma are represented by lesions mainly located in the subcortical structures, and include lacunar infarcts, ischemic white-matter lesions, and intracerebral hemorrhage. An international working group has recently published the STRIVE (STandards for ReportIng Vascular changes on nEuroimaging) to provide definitions and imaging standards for markers and consequences of SVD.2 According to this consensus, changes currently seen on neuroimaging related to SVD include lacunes, recent small subcortical infarcts, white-matter hyperintensities (WMH), perivascular spaces (PVS), microbleeds (MB), and brain atrophy.Over the last few decades, evidence has being accumulated regarding prevalence, clinical significance, and

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“…In addition to H 2 O 2 , SMO produces 3-aminopropanal, a byproduct that contributes to the formation of acrolein, a highly reactive aldehyde. Acrolein associated with elevated polyamine catabolism has been strongly implicated in the etiology of diseases including ischemia-reperfusion injuries, renal failure, stroke, and silent brain infarction (39)(40)(41)(42)(43)(44). Further, elevated SMO expression has been observed in inflammation-associated human diseases including gastritis (22), ulcerative colitis (23), and prostatic intraepithelial neoplasia (24).…”

Section: Resultsmentioning

confidence: 99%

Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis -induced colon tumorigenesis

Goodwin¹,

Shields²,

Wu³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

486

353

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It is estimated that the etiology of 20-30% of epithelial cancers is directly associated with inflammation, although the direct molecular events linking inflammation and carcinogenesis are poorly defined. In the context of gastrointestinal disease, the bacterium enterotoxigenic Bacteroides fragilis (ETBF) is a significant source of chronic inflammation and has been implicated as a risk factor for colorectal cancer. Spermine oxidase (SMO) is a polyamine catabolic enzyme that is highly inducible by inflammatory stimuli resulting in increased reactive oxygen species (ROS) and DNA damage. We now demonstrate that purified B. fragilis toxin (BFT) upregulates SMO in HT29/c1 and T84 colonic epithelial cells, resulting in SMO-dependent generation of ROS and induction of γ-H2A.x, a marker of DNA damage. Further, ETBF-induced colitis in C57BL/6 mice is associated with increased SMO expression and treatment of mice with an inhibitor of polyamine catabolism, N 1 ,N 4 -bis(2,3-butandienyl)-1,4-butanediamine (MDL 72527), significantly reduces ETBF-induced chronic inflammation and proliferation. Most importantly, in the multiple intestinal neoplasia (Min) mouse model, treatment with MDL 72527 reduces ETBF-induced colon tumorigenesis by 69% (P < 0.001). The results of these studies indicate that SMO is a source of bacteria-induced ROS directly associated with tumorigenesis and could serve as a unique target for chemoprevention.inflammatory bowel diseases | adenomatous polyposis coli I t is estimated that chronic inflammation associated with microbial infection directly contributes to the etiology of about 20% of epithelial cancers. The chronic inflammatory microenvironment is characterized by immune dysregulation and elevated levels of reactive oxygen species [ROS; including superoxide, hydrogen peroxide (H 2 O 2 ), and singlet oxygen]. These features result in activation of stress response pathways and oncogenes, down-regulation of tumor suppressor genes, cell and tissue damage, and contribute to tumor initiation, promotion, and progression. However, the precise molecular links between inflammation and carcinogenesis remain to be clarified (1, 2).In the colon, alterations in the physiological balance between the diverse and abundant microbiota (w10 12 organisms per gram feces) and the host are a common source of inflammation. Bacteroides spp comprise a significant proportion of colonic commensal bacteria and members of this group include symbionts and the leading human anaerobic pathogen, Bacteroides fragilis. Enterotoxigenic B. fragilis (ETBF) represent a molecular subtype characterized by a single unique virulence determinant, the production and secretion of a 20-kDa metalloprotease enterotoxin (B. fragilis toxin; BFT). ETBF have been epidemiologically associated with acute diarrheal diseases in humans and livestock, inflammatory bowel diseases (IBD), and colorectal cancer (reviewed in ref.3). Exposure of intestinal epithelial cell lines to BFT results in cleavage of the cell adhesion and tumor suppressor protein E-cadherin, ...

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Acrolein, IL-6 and CRP as markers of silent brain infarction

Cited by 59 publications

References 29 publications

Protein modification by acrolein: Relevance to pathological conditions and inhibition by aldehyde sequestering agents

Protein modification by acrolein: Relevance to pathological conditions and inhibition by aldehyde sequestering agents

Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review

Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis -induced colon tumorigenesis

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