Background: Ascending thoracic aortic aneurysm (aTAA) is a heterogeneous group of disorders that involve impaired endothelial function. The nitric oxide (NO) synthase inhibitor asymmetric dimethylarginine (ADMA) serves as an endothelial dysfunction marker. Thus, we investigated ADMA levels in patients with aTAA. Methods: Eighty-six patients with aTAA and 18 healthy individuals were enrolled. All patients underwent echocardiography. Plasma ADMA levels were measured using high-performance liquid chromatography. Results: ADMA levels were higher in aTAA patients than in control patients (p = 0.034). According to the multivariable regression model, higher ADMA levels were associated with ascending aortic diameter (p = 0.017), smoking (p = 0.016), and log-transformed estimated glomerular filtration rate (eGFR, p = 0.005). Conclusion: This pilot study demonstrates an association of ADMA with ascending aortic dilatation; however, further studies are needed to investigate whether increased ADMA levels underlie aTAA development.
Ultrafiltration rates (filterability) of protein-bound homocysteine (Hcy), unlike glutathione (Glt), are significantly decreased in patients with cardiovascular disorders, end-stage renal disease, and prothrombotic conditions. Reduced filterability of Hcy through 300,000 MWCO PES membranes in these groups of patients was observed, regardless of hyperhomocysteinemia (HHcy) degree. Filterability of Hcy, but not of glutathione, was impaired in plasma preparations. It is possible that the patients with impaired filterability of Hcy in mixed disulfide state are characterized by increased ability of partial Hcy retention by proteins and complexes with higher than albumin molecular weight. These findings led us to conclude that evaluation of protein-bound Hcy filterability may provide more complete diagnostic data, to interpret clinical significance of HHcy. The proposed Hcy filterability test may be performed as a simple laboratory procedure, in addition to conventional tests for total Hcy.
The level of homoarginine (hArg) in terms of prognostic significance may exceed the natriuretic peptides and other well-known markers according to the latest data about the progression of cardiovascular diseases. The lack of data on the association of hArg levels with levels of other metabolites makes it difficult to understand its role in the pathogenesis of cardiovascular diseases. Relationships of hArg and other amino acids, including methionine (Met) and total homocysteine (tHcy), and their ratio in patients with ischemic heart disease were evaluated. The study included 74 patients with coronary heart disease (57 men and 17 women) aged 62 (57 - 67) years before coronary artery bypass surgery and 27 healthy people of similar age. In patients, the level of hArg was almost 2 times lower (p <0.05) than in healthy individuals and rates lower than 1.4 μM were in half of them. The statistically significant decrease (p = 0.0025) of the Met/tHcy ratio corresponded to a decrease in the level of hArg. This ratio did not correlate with glucose level or body mass index. Less statistical significance of hArg correlation with levels of Met or tHcy separately was observed. In the subgroup of patients with hAarg level above 2.1 μM, a lower incidence of myocardial infarction was noted. Thus, a low hArg level is associated with impaired metabolism of sulfur-containing amino acids involved in transmethylation reactions, in patients with ischemic heart disease. The Met/tHcy ratio, closely correlating with the level of hArg, apparently reveals a link between the reactions of creatine formation and transmethylation, highlighting a cohort of patients with the most profound and dangerous changes in tissue metabolism.
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