Suppression of Endothelial Progenitor Cells in Human Coronary Artery Disease by the Endogenous Nitric Oxide Synthase Inhibitor Asymmetric Dimethylarginine

Abstract

Asymmetric dimethylarginine is an endogenous inhibitor of mobilization, differentiation, and function of EPCs. This contributes to the cardiovascular risk in patients with high ADMA levels and may explain low numbers and function of EPCs in patients with coronary artery disease.

Asymmetric Dimethylarginine and Clinical Outcomes in Chronic Kidney Disease

“…In this study, elevated plasma ADMA levels were also observed in patients with macroalbuminuria. Finally, ADMA has been shown to inhibit mobilization, differentiation, and function of endothelial progenitor cells (32), and recently, both ADMA accumulation and epithelial progenitor cell deficiency have been found to synergistically accelerate the deterioration of renal function in patients with stable angina (33). In summary, it may be hypothesized that in patients with mild to moderate CKD, the association between ADMA and long-term adverse events may be attributed to the reducing NO bioavailability/impaired endothelial dysfunction and/or increased oxidative stress and/or suppressed function of endothelial progenitor cells via inhibition of NO synthase and its association with proteinuria.…”

Angiotensin II promotes NO production, inhibits apoptosis and enhances adhesion potential of bone marrow-derived endothelial progenitor cells

“…First, AngII increased eNOS expression and thus NO release. Mobilization and differentiation of EPCs is known to be modified by NO [21]. Observations that mice deficient in eNOS display reduced EPCs mobilization by VEGF and impaired ischemia-induced angiogenesis [22] suggest that eNOS may be required for EPC-induced angiogenesis.…”

Developmental changes in the L-arginine/nitric oxide pathway from infancy to adulthood: plasma asymmetric dimethylarginine levels decrease with age

“…Therefore, numerically the decrease of circulating ADMA concentration by almost 600 nmol/L within the first 20 years of life can be regarded as dramatic in comparison with the increase by only 110 nmol/L of ADMA from 20 to 80 years of age. Nevertheless, small increases in circulating ADMA concentration in adulthood should not be underestimated, because increases of the order of 100 nmol/L in circulating ADMA concentration may be associated with pathologically highly relevant conditions, such as coronary artery disease (38) and other cardiovascular and renal diseases (35)(36)(37). Unlike in circulation, ADMA excretion in urine remained almost unchanged over age ( Figure 2A).…”

“…Children with circulating ADMA concentrations similar to and even higher than those measured in various diseases including renal and cardiovascular diseases (35)(36)(37)(38) are clinically healthy, suggesting that in infancy alternative mechanisms may exist that counteract the inhibitory action of ADMA on NOS. Possible mechanisms could involve participation of potent vasoactive substances from other pathways, such as prostacyclin from the cyclooxygenase pathway.…”