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However, these interactions were prevented in PMNs from T2D patients treated with GLP-1 receptor agonists and were associated with decreased ICAM-1 and VCAM-1 levels in these patients

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In the LURIC study, a single cut-off point (0.8 fmol/ml) of Big-ET-1 was significantly associated with higher incidence rates of cardiovascular death at both intermediate and high NT-proBNP levels.96 In a post hoc analysis of the RELAX trial, plasma ET-1 levels were significantly associated with lower exercise oxygen consumption both at baseline and longitudinally over 24 weeks.97 ET-1 levels were predictive of 1-year HF hospitalisation and were associated with long-term mortality in HFpEF patients ( Table 2 ), suggesting that ET-1 could be a biomarker in HFpEF and a potential therapeutic target.98 Following this, in a prospective study with HFpEF patients, the dual ET-A/ET-B receptor inhibitor macitentan improved HFpEF by abrogating adverse cardiac remodelling via antihypertrophic mechanisms and by reducing stiffness.99 In the same population, sitaxsentan, a selective ET-A receptor antagonist, increased exercise tolerance but did not improve any of the secondary endpoints such as LV mass or diastolic function.100 Plasminogen Activator Inhibitor-1 Plasminogen activator inhibitor-1 (PAI-1) is a serine protease inhibitor that functions as the principal inhibitor of tissue plasminogen activator and urokinase, the activators of plasminogen and hence fibrinolysis

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