Role of asymmetrical dimethylarginine in inflammation-induced endothelial dysfunction in human atherosclerosis.

Abstract

We explored the role of asymmetrical dimethylarginine (ADMA) as a cause of endothelial dysfunction induced by systemic inflammation. In vitro data suggest that ADMA bioavailability is regulated by proinflammatory stimuli, but it is unclear whether ADMA is a link between inflammation and endothelial dysfunction in humans. In study 1 we recruited 351 patients with coronary artery disease (CAD) and 87 healthy controls. In study 2 we recruited 69 CAD, 69 healthy, and 10 patients with rheumatoid arthritis, whereas in study 3, 22 healthy and 70 CAD subjects were randomly assigned to Salmonella typhii vaccination (n=11 healthy and n=60 CAD) or placebo (n=11 healthy and n=10 CAD). Circulating interleukin 6/ADMA and flow-mediated dilation (FMD) were measured at 0 and 8 hours. In study 1, ADMA was inversely correlated with FMD in healthy individuals and CAD patients (P<0.0001 for both). However, interleukin 6 was inversely correlated with FMD (P<0.0001) in healthy subjects but not in CAD patients. The positive correlation between ADMA and interleukin 6 was stronger in healthy (r=0.515; P<0.0001) compared with CAD (r=0.289; P=0.0001) subjects. In study 2, both patients with rheumatoid arthritis and CAD had higher interleukin 6 (P<0.0001) and ADMA (P=0.004) but lower FMD (P=0.001) versus healthy subjects. In study 3, vaccination increased interleukin 6 in healthy (P<0.001) and CAD (P<0.001) subjects. FMD was reduced in healthy subjects (P<0.05), but its reduction in CAD was borderline. Vaccination increased ADMA only in healthy subjects (P<0.001). Systemic, low-grade inflammation leads to increased ADMA that may induce endothelial dysfunction. This study demonstrated that ADMA may be a link between inflammation and endothelial dysfunction in humans.

• Authors: Charalambos Antoniades, Michael Demosthenous, Dimitris Tousoulis, Alexios S Antonopoulos, Charalambos Vlachopoulos, Marina Toutouza, Kyriakoula Marinou, Constantinos Bakogiannis, Kleio Mavragani, George Lazaros, Nikolaos Koumallos, Costas Triantafyllou, Dimitris Lymperiadis, Michael Koutsilieris, Christodoulos Stefanadis
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 58 Issue 1 Pg. 93-8 (Jul 2011) ISSN: 1524-4563 [Electronic] United States
• PMID: 21518967 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• dimethylarginine
• Arginine

Topics

• Arginine (analogs & derivatives, blood)
• Atherosclerosis (blood, etiology, physiopathology)
• Coronary Artery Disease (blood, etiology, physiopathology)
• Disease Progression
• Endothelium, Vascular (physiopathology)
• Female
• Follow-Up Studies
• Humans
• Inflammation (blood, complications, physiopathology)
• Male
• Pilot Projects
• Prognosis
• Vasodilation (physiology)