Browsing by Author "Korzh, Stanislava"

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    Inhibition of Fatty Acid Metabolism Increases EPA and DHA Levels and Protects against Myocardial Ischaemia-Reperfusion Injury in Zucker Rats
    (2021-07-29) Kuka, Janis; Makrecka-Kuka, Marina; Vilks, Karlis; Korzh, Stanislava; Cirule, Helena; Sevostjanovs, Eduards; Grinberga, Solveiga; Dambrova, Maija; Liepinsh, Edgars; Faculty of Pharmacy
    Long-chain ω-3 polyunsaturated fatty acids (PUFAs) are known to induce cardiometabolic benefits, but the metabolic pathways of their biosynthesis ensuring sufficient bioavailability require further investigation. Here, we show that a pharmacological decrease in overall fatty acid utilization promotes an increase in the levels of PUFAs and attenuates cardiometabolic disturbances in a Zucker rat metabolic syndrome model. Metabolome analysis showed that inhibition of fatty acid utilization by methyl-GBB increased the concentration of PUFAs but not the total fatty acid levels in plasma. Insulin sensitivity was improved, and the plasma insulin concentration was decreased. Overall, pharmacological modulation of fatty acid handling preserved cardiac glucose and pyruvate oxidation, protected mitochondrial functionality by decreasing long-chain acylcarnitine levels, and decreased myocardial infarct size twofold. Our work shows that partial pharmacological inhibition of fatty acid oxidation is a novel approach to selectively increase the levels of PUFAs and modulate lipid handling to prevent cardiometabolic disturbances.
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    Protective effects of meldonium in experimental models of cardiovascular complications with a potential application in COVID‐19
    (2022-01-01) Vilskersts, Reinis; Kigitovica, Dana; Korzh, Stanislava; Videja, Melita; Vilks, Karlis; Cirule, Helena; Skride, Andris; Makrecka‐Kuka, Marina; Liepinsh, Edgars; Dambrova, Maija; Department of Pharmaceutical Chemistry; Department of Internal Diseases
    Right ventricular (RV) and left ventricular (LV) dysfunction is common in a significant number of hospitalized coronavirus disease 2019 (COVID‐19) patients. This study was conducted to assess whether the improved mitochondrial bioenergetics by cardiometabolic drug meldonium can attenuate the development of ventricular dysfunction in experimental RV and LV dysfunction models, which resemble ventricular dysfunction in COVID‐19 patients. Effects of meldonium were assessed in rats with pulmonary hypertension‐induced RV failure and in mice with inflammation-induced LV dysfunction. Rats with RV failure showed decreased RV fractional area change (RVFAC) and hypertrophy. Treatment with meldonium attenuated the development of RV hyper-trophy and increased RVFAC by 50%. Mice with inflammation‐induced LV dysfunction had decreased LV ejection fraction (LVEF) by 30%. Treatment with meldonium prevented the decrease in LVEF. A decrease in the mitochondrial fatty acid oxidation with a concomitant increase in pyruvate metabolism was noted in the cardiac fibers of the rats and mice with RV and LV failure, respectively. Meldonium treatment in both models restored mitochondrial bioenergetics. The results show that meldonium treatment prevents the development of RV and LV systolic dysfunction by enhancing mitochondrial function in experimental models of ventricular dysfunction that resembles cardiovascular complications in COVID‐19 patients.