The vulnerable vessel

Summary

Diabetes represents one of the most important risk factors for atherosclerosis, which is the leading cause of mortality worldwide. Recent imaging studies employing intravascular ultrasound or computed coronary angio - graphy tomography clearly confirm that diabetes is associated with larger plaque burden and with more lesions displaying features of instability. Various molecular mechanisms promoting atherogenesis and plaque destabilization in diabetics have been described in the past. The current review specifically focuses on recent papers that have addressed the effects of diabetes and hyperglycemia (i) on myeloid cells, (ii) on oxidative stress, and (iii) on protein kinase C (PKC) activation. Thus, it has been demonstrated that hyperglycemia may promote myelopoiesis and differentiation of pro-inflammatory macrophages. Furthermore, novel studies emphasize the interplay between inflammation and oxidative stress at both the molecular and the genetic level. Finally, experimental studies shed light on the role of PKC-_ in diabetes-associated atherosclerosis. Several of these recent studies suggest that atherogenesis and plaque destabilization in diabetic individuals may be mediated by diabetes-specific mechanisms. This may open the door for developing tailored anti-atherosclerotic therapies for diabetic patients.

Zusammenfassung

Diabetes ist einer der wichtigsten Risikofaktoren für die Entwicklung einer Atherosklerose, der führenden Todesursache weltweit. In den letzten Jahren veröffentlichte Studien, die mittels neuer bildgebender Verfahren wie intravaskulärem Ultraschall oder Computertomographie die Koronarien diabetischer Patienten untersucht haben, zeigen, dass Diabetiker mehr Plaquelast, aber auch instabilere Plaques aufweisen als nicht-diabetische Kontrollpatienten. Es gibt eine große Zahl molekularer Mechanismen, die diesem Phänomen zugrunde liegen. Hier werden spezifisch neuere Arbeiten referiert, die die Effekte von Diabetes und Hyperglykämie (i) auf die myeloide Zellreihe, (ii) auf die Entwicklung von oxidativem Stress sowie (iii) auf die Aktivierung von Isoformen der Proteinkinase C (PKC) untersucht haben. So konnte gezeigt werden, dass Hyperglykämie die Myelopoiese fördert und gleichzeitig die Differenzierung pro-inflammatorischer Makrophagen begünstigt. Weiterhin demonstrieren neue Studien das Wechselspiel zwischen Inflammation und oxidativem Stress auf molekularer wie auch genetischer Ebene. Schließlich beleuchten neue Studien die Rolle der PKC-βim Rahmen der Diabetes-assoziierten Atherosklerose. Einige dieser aktuellen Studien legen nahe, dass es Diabetes-spezifische Patho mechanismen der Plaque-Entstehung und -Destabilisierung gibt. Dies könnte die Grundlage für neue Therapieansätze darstellen, die spezifisch die Atherosklerose des Diabetikers adressieren.

Keywords

Diabetes mellitus - atherosclerosis - protein kinase C

Schlüsselwörter

Diabetes mellitus - Atherosklerose - Monozyten - oxidativer Stress - Proteinkinase C

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