0000000000053945
AUTHOR
Karsten Sydow
Endothelium- and nitric oxide-dependent vasorelaxing activities of gamma-butyrobetaine esters: possible link to the antiischemic activities of mildronate.
Mildronate [3-(2,2,2-trimethylhydrazine) propionate (THP)] is an antiischemic drug acting mainly via inhibition of fatty acid beta-oxidation. Some effects of the drug cannot be explained by the latter mechanism. We tested the eventual nitric oxide (NO) dependence of the mildronate action. Mildronate, gamma-butyrobetaine (GBB) and GBB methyl ester induced transient increases in nitric oxide (NO) concentrations in rat blood and myocardium. In vitro, these compounds neither modified the activities of purified neuronal and endothelial recombinant nitric oxide synthases (NOSs) nor were able to interact with their active site. GBB induced vasodilatation at high concentrations only (EC50 = 5 x 10(…
Association of MR-proadrenomedullin with cardiovascular risk factors and subclinical cardiovascular disease.
Abstract Aims and background Midregional proadrenomedullin (MR-proADM) is a protein, which exerts various effects on the cardiovascular system. Recent studies underscored its prognostic implications in patients with acute dyspnea and cardiovascular diseases. Therefore, we aimed to determine the distribution of MR-proADM in the general population and to reveal potential associations of MR-proADM with cardiovascular risk factors and measures of subclinical cardiovascular disease. Methods and results MR-proADM plasma concentrations were determined in individuals of the population-based cohort of the Gutenberg Health Study ( N = 5000) using a commercially available fluoroimmunoassay. Individua…
Extensive characterization of the human DDAH1 transgenic mice
Abstract Purpose of the research Overexpression of the human dimethylarginine dimethylaminohydrolase type 1 (hDDAH1) gene was reported to have beneficial cardiovascular effects in mice. To date, it is unclear whether these effects are related to enhanced metabolic clearance of asymmetric dimethylarginine (ADMA) and l - N G -mono-methyl- l -arginine ( l -NMMA) or increased DDAH1 expression and activity in cardiovascular tissues of hDDAH1 transgenic mice. Principal results DDAH activity (DDAH1 + DDAH2) was found to be markedly increased in aortic and heart tissues but unaltered in liver and kidney tissues of hDDAH1 transgenic as compared to wild-type (WT) mice. In WT mice, DDAH activity was m…
Differential effects of diabetes on the expression of the gp91phox homologues nox1 and nox4.
The nox2-dependent NADPH oxidase was shown to be a major superoxide source in vascular disease, including diabetes. Smooth muscle cells of large arteries lack the phagocytic gp91phox subunit of the enzyme; however, two homologues have been identified in these cells, nox1 and nox4. It remained to be established whether also increases in protein levels of the nonphagocytic NADPH oxidase contribute to increased superoxide formation in diabetic vessels. To investigate changes in the expression of these homologues, we measured their expression in aortic vessels of type I diabetic rats. Eight weeks after streptozotocin treatment, we found a doubling in nox1 protein expression, while the expressio…
Effects of alirocumab on types of myocardial infarction : insights from the ODYSSEY OUTCOMES trial
Gislason, Gunnar H/0000-0002-0548-402X; Malynovsky, Yaroslav V/0000-0002-9118-1104; Bhatt, Deepak L./0000-0002-1278-6245; Nikolaev, Konstantin/0000-0003-4601-6203; Sherwood, Matthew/0000-0002-4305-5883; Chumakova, Galina A/0000-0002-2810-6531; Raffel, Owen C/0000-0001-5470-7050; Leonardi, Sergio/0000-0002-4800-6132; Tse, Hung Fat/0000-0002-9578-7808; Reshetko, Olga/0000-0003-3107-7636; Pereira, Helder/0000-0001-8656-4883; Racca, Vittorio/0000-0002-4465-3789; Podoleanu, Cristian/0000-0001-9987-2519; Ersanli, Murat/0000-0003-1847-3087; Muenzel, Thomas/0000-0001-5503-4150; Sandhu, Manjinder/0000-0003-2538-2079; Taskinen, Marja-Riitta/0000-0002-6229-3588; bastos, jose/0000-0002-9526-3123; Manak…