Expression of the aging gene p66Shc is increased in peripheral blood monocytes of patients with acute coronary syndrome but not with stable coronary artery disease

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• 作者：Fabian C. Franzeck^a ; ¹ ; Danielle Hof^b ; ¹ ; Remo D. Spescha^c ; ^d ; ¹ ; Matthias Hasun^a ; Alexander Akhmedov^c ; ^d ; Jan Steffel^c ; ^d ; Yi Shi^c ; ^d ; Francesco Cosentino^c ; ^d ; Felix C. Tanner^c ; ^d ; Arnold von Eckardstein^b ; ^d ; Willibald Maier^a ; Thomas F. Lü ; scher^a ; ^c ; ^d ; Christophe A. Wyss^a ; Giovanni G. Camici^c ; ^d ; ^{giovannic@access.uzh.ch}
• 关键词：p66shc ; Oxidative stress ; Coronary artery disease ; Acute coronary syndrome
• 刊名：Atherosclerosis
• 出版年：2012
• 出版时间：January 2012
• 年：2012
• 卷：220
• 期：1
• 页码：282-286
• 全文大小：162 K

文摘

Objective

The interplay between oxidative stress and inflammation is crucial in the pathogenesis of atherosclerosis. The adaptor protein p66Shc is implicated in atherogenesis and oxidative stress related responses in animal models of diseases. However, its role in humans remains to be defined. In this study, we hypothesized that expression of p66Shc increases in peripheral blood monocytes of patients affected by acute coronary syndromes (ACS).

Methods

Male subjects aged 59 ¡À 4 (mean ¡À SD) years admitted for cardiac catheterization were subdivided in three groups: (a) no local stenosis for the control group, (b) at least one stenosis ?5 % in either left, circumflex or right coronary artery for the coronary artery disease (CAD) group or (c) ST-elevation/non-ST-elevation myocardial infarction for the ACS group. Monocytes were isolated from whole blood and p66Shc RNA levels were determined by quantitative real time PCR.

Results

p66Shc RNA levels were increased in ACS patients as compared to CAD (p = 0.007) and controls (p = 0.0249). Furthermore, malondialdehyde (MDA) and C-reactive protein (CRP) were increased in plasma of ACS patients. Levels of MDA correlated positively to p66Shc (r = 0.376, p = 0.01). Our data demonstrate increased p66Shc levels in monocytes of ACS but not CAD patients.

Conclusion

This study suggests an involvement of p66Shc in the transition of a stable CAD to an ACS patient. p66Shc was associated with states of increased oxidative stress. Further work is needed to understand whether p66Shc may represent a possible pharmacological target or whether it represents an interesting novel biomarker.