Search for: [Abstract = "ICs cultured under different conditions was assessed at the protein and mRNA \(SERPINE1\) levels. Mechanistic studies were performed using an inhibitor of PAI\-1 activity \(TM5275\) or an NF\-κB pathway inhibitor \(BAY 11\-7082\). VICs culture supernatants were added to PAI\-1 – depleted plasma, and CLT was measured using a modified method. The level of PAI\-1 antigen in the supernatants was determined using an ELISA test. Valvular expression of PAI\-1, which correlated with lipid accumulation, NF\-κB expression, and the severity of AS, was observed only in stenotic aortic valves. In vitro, VICs showed high PAI\-1 expression. LDL stimulation increased the level of PAI\-1 in VICs supernatants and prolonged CLT. Inhibition of PAI\-1 activity shortened CLT, while inhibition of the NF\-κB pathway reduced PAI\-1 expression in VICs, the level of its antigen in supernatants, and shortened CLT. Analysis of mRNA expression \(SERPINE1\) in VICs confirmed these results. Publication 5 discusses the latest potential therapeutic strategies for inhibiting the progression of AS. Conclusions In patients with AS and concomitant poorly controlled DMT2, uncontrolled diabetes leads to excessive accumulation of AGEs in aortic valves, thereby exacerbating local oxidative stress, inflammation, and the synthesis of valvular calcification mediators, ultimately resulting in faster progression of AS. Hypergly"]

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