Asymmetric Dimethyl Arginine as a Biomarker of Atherosclerosis in Rheumatoid Arthritis

Table 2

ADMA lowering effect and possible pharmacodynamic mechanism of different drugs.

Drug	Investigated conditions	Hypothesized mechanism	Results	References
Statins	Diabetes mellitus, stroke, hypercholesterolemia	Increase DDAH expression, increased bioavailability of tetrahydrobiopterin	Decreased ADMA serum levels (18–50%)	[100, 109]
Fibrate	Hypertriglyceridemia	Increase DDAH activity through NF-kB suppression via PPAR-α receptors	Uncertain effect on ADMA serum levels, increase L-arginine/ADMA ratio	[111]
Niacine	Dyslipidemia	Depletion of methyl groups for niacine metabolism and consequent reduction in ADMA synthesis	Decreased ADMA serum levels (10%)	[112]
ACE inhibitors/ARB	Chronic glomerulonephritis, hypertension	Decreased NADPH oxidase upregulation by RAA system, with consequent reduced ROS-mediated DDAH inhibition	Decreased ADMA serum levels (10–16%)	[113, 114]
Thiazolidinediones	Diabetes mellitus	Through PPAR-γ receptor activation: reduced insulin resistance, increased expression of DDAH in renal tubules, suppressed activity of NF-kB	Controversial; from no reduction to reduction of ADMA serum levels (10%), possible protection against ADMA effect	[115]
Metformin	Diabetes mellitus; Polycystic ovarian syndrome	Partially unknown, apparently not mediated by PRTM or DDAH; Competitive antagonist of ADMA	Decreased ADMA serum levels (27%)	[116]
Nebivolol	Hypertension	Upregulation of DDAH, downregulation of PRTM	Decreased ADMA serum levels (37–44%)	[117, 118]
Acetylsalicylic acid	Coronary artery disease	Upregulation of DDAH and eNOS	Decreased ADMA serum levels (30%)	[119]
Estrogens	Postmenopausal women	Upregulation of DDAH via ERα	Decreased ADMA serum levels (18–20%)	[120, 121]
Folate and B group vitamins	Hypertension, hyperhomocysteinemia, chronic heart failure	Increased bioavailability of methylenetetrahydrofolate	Decreased ADMA serum levels (14%), acute decrease during e.v. infusion	[122, 123]
α-Lipoic acid	End-stage renal disease, diabetes mellitus	Activation and upregulation of DDAH via STAT3	Decreased ADMA serum levels (9%)	[124]
N-Acetylcysteine	End-stage renal disease	Partially unknown, direct activation DDAH, or ROS scavenging	Decreased ADMA serum levels (30%)	[125]