Associations of Serum IL-18 Levels With Carotid Intima-Media Thickness

Yamagami, Hiroshi; Kitagawa, Kazuo; Hoshi, Taku; Furukado, Shigetaka; Hougaku, Hidetaka; Nagai, Yoji; Hori, Masatsugu

doi:10.1161/01.atv.0000168417.52486.56

Cited by 118 publications

(75 citation statements)

References 41 publications

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“…Increased levels of IL-18 have been found in various autoimmune and inflammatory diseases including patients with heart failure and coronary artery disease where its levels correlate with disease severity [1][2][3][4][5][6]. In these patients, a concomitant increase in IL-18 binding protein (IL-18BP) is observed [6] IL-18BP is a naturally occurring inhibitor of IL-18, is detected in the plasma of healthy subjects at 10-to 20-fold molar excess over IL-18 [7], and is decreased in patients with myocardial ischemic injury and dilated cardiomyopathy.…”

Section: Introductionmentioning

confidence: 99%

Carbon monoxide donors or heme oxygenase-1 (HO-1) overexpression blocks interleukin-18-mediated NF-κB–PTEN-dependent human cardiac endothelial cell death

Zabalgoitia

Colston

Reddy

et al. 2008

Free Radical Biology and Medicine

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The objective of this study was to determine whether heme oxygenase-1 (HO-1) or heme metabolites exert cytoprotective effects on interleukin-18-mediated endothelial cell (EC) death. Treatment with IL-18 increased NF-κB activation, PTEN induction, suppressed Akt activation, and stimulated EC death. While ectopic expression of p65 enhanced PTEN transcription, adenoviral transduction of dnIκB-α, dnp65, or dnIKKβ was inhibitory. Furthermore, IL-18 suppressed HO-1 mRNA expression via enhanced mRNA degradation. Overexpression of HO-1, treatment with HO-1 inducer hemin or the CO donor Cobalt (III) protoporphyrin IX all reversed IL-18-mediated NF-κB activation, PTEN induction, Akt suppression, and EC death. Furthermore, hemin induced HO-1 expression, and HO-1 knockdown, HO-1 inhibition, or CO scavengers all reversed the pro-survival effects of hemin. In addition, the CO donors CORM-1 and CORM-3 and the heme metabolites biliverdin and bilirubin attenuated IL-18-induced EC death via a similar signaling pathway. IL-18 induced p38α MAPK activation, and suppressed p38β isoform expression. While p38α knockdown attenuated, p38β knockdown potentiated IL-18-mediated EC death. Hemin and HO-1 reversed IL-18-mediated p38α induction, and restored p38β levels. These results demonstrate that IL-18 suppresses HO-1 expression and induces EC death. HO-1 overexpression, HO-1 induction, or treatment with heme metabolites all reverse IL-18-mediated p38α MAPK and NF-κB activation, PTEN induction, Akt suppression, and EC death. Thus, HO-1 inducers and CO donors may have the therapeutic potential to effectively block IL-18 signaling and reduce IL-18-dependent vascular injury and inflammation.

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Section: Introductionmentioning

confidence: 99%

Carbon monoxide donors or heme oxygenase-1 (HO-1) overexpression blocks interleukin-18-mediated NF-κB–PTEN-dependent human cardiac endothelial cell death

Zabalgoitia

Colston

Reddy

et al. 2008

Free Radical Biology and Medicine

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“…In their study, they demonstrated association of higher serum IL-18 levels with greater carotid intima-media thickness (IMT) (as evaluated by Bmode ultrasound), suggesting a link between IL-18 and atherosclerosis. In addition, findings of Yamagami et al (2005) reported a positive association of serum IL-18 with other predictive risks like age and BMI in subjects with coronary heart disease [42].…”

Section: Interleukin 18 As Biomarker In Atherosclerosismentioning

confidence: 96%

“…One of the earlier studies, by Mallat et al [26] and Yamagami et al [42] has shown the importance of IL-18 as biomarker of the disease. In their study, they demonstrated association of higher serum IL-18 levels with greater carotid intima-media thickness (IMT) (as evaluated by Bmode ultrasound), suggesting a link between IL-18 and atherosclerosis.…”

Section: Interleukin 18 As Biomarker In Atherosclerosismentioning

confidence: 97%

Interleukin-18 and Atherosclerosis: Mediator or Biomarker

Mahajan¹

2014

J Clin Exp Cardiolog

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Atherosclerosis, a progressive disorder of the vessel walls with the formation of plaques throughout the arterial system, is an essential pathological process in the development of various Cardiovascular Diseases (CVDs). Inflammation has been demonstrated to play an inevitable role in all the stages of atherosclerosis though its pathogenesis is complicated and still remains enigmatic. Interleukin-18 (IL-18) is a pleiotropic pro-inflammatory cytokine, which belongs to the Interleukin-1 (IL-1) family. This pro-inflammatory cytokine is among the more recently recognized cytokines to be involved in the development of various cardiovascular diseases and their related manifestations. At one end, studies indicate that IL-18 is a key player that orchestrates the inflammatory cascade associated with the pathogenesis of atherosclerosis, whereas others showed circulating levels of IL-18 to be a prognostic marker. Present article summarizes the scientific rationale which highlights the signatures of interleukin-18 as a mediator in the pathogenesis as well as a diagnostic marker.

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“…20 Mean carotid intima-media thickness (mean IMT) and plaque score were calculated as previously described. 21,22 These recordings and measurements were performed by sonographers from Advanced Harmonic Information Technology , Osaka, Japan, who were unaware of the study group assignment.…”

Section: Data Collectionmentioning

confidence: 99%

The Effect of Losartan and Amlodipine on Left Ventricular Diastolic Function and Atherosclerosis in Japanese Patients with Mild-to-Moderate Hypertension (J-ELAN) study

Yamamoto

Ozaki²,

Takayasu

et al. 2010

Hypertens Res

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This study was a prospective, randomized, open, blinded endpoint study to assess the effects of angiotensin II type 1 receptor blocker, losartan, compared with calcium channel blocker, amlodipine, on left ventricular (LV) diastolic function and atherosclerosis of the carotid artery in Japanese patients with mild-to-moderate hypertension, LV hypertrophy, diastolic dysfunction and preserved systolic function. Fifty-seven patients were randomly assigned to losartan-or amlodipine-based treatment groups and were followed up for 18 months. Blood pressure was similarly reduced by both regimens. Losartan shortened the transmitral E-wave deceleration time, and amlodipine reduced LV mass index; however, there was no significant difference in the percent changes of these indices between the two groups. Mean carotid intima-media thickness (mean IMT) as well as plaque score significantly increased in the amlodipine-based regimen (pre: 1.05 ± 0.26 mm, follow-up: 1.23 ± 0.33 mm, P¼0.0015), but not in the losartan-based regimen (pre: 1.08 ± 0.35 mm, follow-up: 1.16 ± 0.52 mm, P¼non-significant). The percent increase in mean IMT in the amlodipine-based regimen tended to be large compared with the losartan-based regimen (amlodipine: 19.8 ± 23.7%, losartan: 6.9 ± 23.3%, P¼0.06). Under similar reduction of blood pressure, losartan is likely effective in protecting the progression of atherosclerosis of the carotid artery compared with amlodipine. Losartan may improve LV diastolic function, and amlodipine may attenuate LV hypertrophy; however, this study cannot make consecutive remarks about the superiority of either treatment regimen in the effects on cardiac function and geometry. This study has been registered at

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Associations of Serum IL-18 Levels With Carotid Intima-Media Thickness

Cited by 118 publications

References 41 publications

Carbon monoxide donors or heme oxygenase-1 (HO-1) overexpression blocks interleukin-18-mediated NF-κB–PTEN-dependent human cardiac endothelial cell death

Carbon monoxide donors or heme oxygenase-1 (HO-1) overexpression blocks interleukin-18-mediated NF-κB–PTEN-dependent human cardiac endothelial cell death

Interleukin-18 and Atherosclerosis: Mediator or Biomarker

The Effect of Losartan and Amlodipine on Left Ventricular Diastolic Function and Atherosclerosis in Japanese Patients with Mild-to-Moderate Hypertension (J-ELAN) study

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