Abstract
ObjectivesAsymmetric- and symmetric dimethylarginines (ADMA, SDMA) are elevated in cardiovascular disease (CVD). Preeclampsia is a pregnancy-specific syndrome and is an independent risk factor for subsequent CVD. Aims were to investigate whether ADMA, SDMA levels and l-arginine/ADMA and l-arginine/SDMA ratios during pregnancy and their changes from pregnancy to postpartum are associated to arterial wall layer dimensions and cardiovascular risk factors in women with and without preeclampsia. Study designDimethylarginines were analyzed by LC–MS, and the common-carotid-artery (CCA) intima and media thicknesses were estimated using 22-MHz non-invasive ultrasonography in women with preeclampsia (cases = 48) and normal pregnancies (controls = 58) in similar gestational age, with reassessment one-year postpartum. A thick intima, thin media and high intima/media ratio (I/M) indicates a less healthy arterial wall. ResultsThe median age of cases and controls was 30 years. During pregnancy, women with preeclampsia had higher plasma ADMA, SDMA and lower l-arginine/ADMA and l-arginine/SDMA (all p < 0.01) than women with normal pregnancies. Further, ADMA, SDMA, l-arginine/ADMA and l-arginine/SDMA correlated to intima thickness (rs = 0.33/0.33/−0.33/−0.35 and p < 0.01), I/M (rs = 0.26/0.28/−0.22/−0.26 and p < 0.05) and mean arterial pressure (MAP) (rs = 0.43/0.42/−0.39/−0.40 and p < 0.0001). Changes in ADMA, SDMA and l-arginine/SDMA from pregnancy to postpartum correlated to changes in intima thickness (rs = 0.22/0.32/-0.21 and p < 0.05/<0.01/<0.05), I/M (rs = 0.22/0.31/0.08 and p < 0.05/<0.01/=0.43) and MAP (rs = 0.31/0.53/-0.25 and p < 0.01/<0.001/<0.05). No correlations were found for conventional CCA intima-media-thickness. ConclusionsDimethylarginines were associated to signs of adverse effects on arterial wall layer dimensions and cardiovascular risk factors in women with and without preeclampsia, during pregnancy and to their changes from pregnancy up to one-year postpartum.
Highlights
Dimethylarginines, asymmetric (ADMA) and symmetric (SDMA) are naturally occurring amino acids in plasma and generated by degradation of methylated protein as a result of protein arginine methyltransferase [1]
We previously showed that the imaging of CCA by 20À25 MHz ultrasound and the use of intima thickness and intima/media thickness ratio (I/M), instead of CCAIMT better image vascular effects in those with prevalent cardiovascular disease (CVD), diabetes mellitus, hypertension and hyperlipidemia [17,18,19], as well as more subclinical atherosclerosis in women with PE, at diagnosis, at one-year postpartum and at seven-year follow-up [20,21]
We aimed to investigate whether dimethylarginines during pregnancy and their changes from pregnancy up to about oneyear postpartum are associated to CCA wall layer dimensions and cardiovascular risk factors in women with and without PE, because such studies are lacking
Summary
Dimethylarginines, asymmetric (ADMA) and symmetric (SDMA) are naturally occurring amino acids in plasma and generated by degradation of methylated protein as a result of protein arginine methyltransferase [1]. Dimethylarginines is a direct endogenous inhibitor of nitric oxide synthase (NOS), which leads to decreased nitric oxide (NO) synthesis. Dimethylarginines may reduce NO synthesis indirectly by inhibiting the cellular uptake of the NO precursor L-arginine [1]. NO is a potent vasodilator, generated in the vessel endothelium from L-arginine by the NOS enzyme [1]. Elevated dimethylarginines levels are associated with decreased NO levels, which leads to endothelial dysfunction and development of atherosclerosis [2,3]. Plasma levels of dimethylarginines are increased in patients with cardiovascular disease (CVD) [4,5]
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