Elevated Levels of Asymmetric Dimethylarginine (ADMA) in the Pericardial Fluid of Cardiac Patients Correlate with Cardiac Hypertrophy

Abstract

BackgroundPericardial fluid (PF) contains several biologically active substances, which may provide information regarding the cardiac conditions. Nitric oxide (NO) has been implicated in cardiac remodeling. We hypothesized that L-arginine (L-Arg) precursor of NO-synthase (NOS) and asymmetric dimethylarginine (ADMA), an inhibitor of NOS, are present in PF of cardiac patients and their altered levels may contribute to altered cardiac morphology.MethodsL-Arg and ADMA concentrations in plasma and PF, and echocardiographic parameters of patients undergoing coronary artery bypass graft (CABG, n = 28) or valve replacement (VR, n = 25) were determined.ResultsWe have found LV hypertrophy in 35.7% of CABG, and 80% of VR patients. In all groups, plasma and PF L-Arg levels were higher than that of ADMA. Plasma L-Arg level was higher in CABG than VR (75.7±4.6 μmol/L vs. 58.1±4.9 μmol/L, p = 0.011), whereas PF ADMA level was higher in VR than CABG (0.9±0.0 μmol/L vs. 0.7±0.0 μmol/L, p = 0.009). L-Arg/ADMA ratio was lower in the VR than CABG (VRplasma: 76.1±6.6 vs. CABGplasma: 125.4±10.7, p = 0.004; VRPF: 81.7±4.8 vs. CABGPF: 110.4±7.2, p = 0.009). There was a positive correlation between plasma L-Arg and ADMA in CABG (r = 0.539, p = 0.015); and plasma and PF L-Arg in CABG (r = 0.357, p = 0.031); and plasma and PF ADMA in VR (r = 0.529, p = 0.003); and PF L-Arg and ADMA in both CABG and VR (CABG: r = 0.468, p = 0.006; VR: r = 0.371, p = 0.034). The following echocardiographic parameters were higher in VR compared to CABG: interventricular septum (14.7±0.5 mm vs. 11.9±0.4 mm, p = 0.000); posterior wall thickness (12.6±0.3 mm vs. 11.5±0.2 mm, p = 0.000); left ventricular (LV) mass (318.6±23.5 g vs. 234.6±12.3 g, p = 0.007); right ventricular (RV) (33.9±0.9 cm2 vs. 29.7±0.7 cm2, p = 0.004); right atrial (18.6±1.0 cm2 vs. 15.4±0.6 cm2, p = 0.020); left atrial (19.8±1.0 cm2 vs. 16.9±0.6 cm2, p = 0.033) areas. There was a positive correlation between plasma ADMA and RV area (r = 0.453, p = 0.011); PF ADMA and end-diastolic (r = 0.434, p = 0.015) and systolic diameter of LV (r = 0.487, p = 0.007); and negative correlation between PF ADMA and LV ejection fraction (r = -0.445, p = 0.013) in VR.ConclusionWe suggest that elevated levels of ADMA in the PF of patients indicate upregulated RAS and reduced bioavailability of NO, which can contribute to the development of cardiac hypertrophy and remodeling.

Nitric Oxide-Related Biological Pathways in Patients with Major Depression

“…However, an elevated ADMA level might increase the risk of fatal events due to cardiovascular diseases [ 30 ]. In addition, elevated levels of ADMA in the pericardial fluid of cardiac patients correlate with cardiac hypertrophy [ 31 ].…”

L-Arginine-Nitric Oxide-Asymmetric Dimethylarginine Pathway and the Coronary Circulation: Translation of Basic Science Results to Clinical Practice

“…Recently, however, it was discovered that many biologically active molecules are also present in the PF ( Figure 6) (Szokodi et al, 1998;Kawamoto et al, 2013). Nemeth et al (2015a) investigated 28 patients undergoing CABG surgery, 25 undergoing valve replacement (VR) (Bosmans et al, 1999), and 20 non-cardiac patients (NCP). Plasma was collected from NCP, while both plasma and pericardial fluid were harvested from patients after median sternotomy.…”

Biomarcadores de função endotelial em doenças cardiovasculares: hipertensão

“…Currently, there is interest in degradation of ADMA by dimethylarginine dimethylaminohydrolase (DDAH), 45 which is constituted by two isoforms (DDAH-1 and DDAH-2). Degradation of ADMA by the enzymatic isoform DDAH-1 takes place in tissues 46 and it has been suggested that modulation of DDAH-1 activity by agonists of the farnesoid X receptor (FXR), for example -(2,6-dichlorophenyl)-4-(3'-carboxy-2-chlorostilben-4-yl) oxymethyl-5-isopropylisoxazole (GW4064), could be used as a therapeutic target in treatments for congestive heart failure and other CVDs.…”

“…According to Nemeth et al, 45 elevated ADMA levels in the pericardial liquid of cardiac patients may be indicative of important pathophysiologic mechanisms, such as reduction in bioavailability of NO, contributing to the development of cardiac hypertrophy and remodeling. These authors therefore propose that analysis of this liquid could be used as a diagnostic tool because of interference in the content and effects of pericardial liquid, opening up new treatment options to beneficially modify cardiac function and structure.…”