Proinflammatory cytokines in acute myocardial infarction with and without cardiogenic shock

Background: Inflammatory response is an important feature of acute coronary syndromes and myocardial infarction (MI). The prognostic value of proinflammatory cytokines in patients with acute MI complicated by cardiogenic shock is unknown. Methods and results: In 41 patients admitted with acute MI (age 60 ± 11 years, six females, 19 Killip class IV) serial plasma concentration of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and interleukin 1 receptor antagonist (IL-1Ra) were measured. Seven patients with cardiogenic shock (CS) developed a systemic inflammatory response syndrome (SIRS). Patients with CS—particularly those who developed SIRS—showed significantly higher cytokine levels than patients with uncomplicated MI. In patients with CS and SIRS peak levels of IL-1Ra were 223,973 pg/ml, IL-6 252.8 pg/ml and TNF-α 7.0 pg/ml. In CS without SIRS IL-1Ra levels were 19,988 pg/ml, IL-6 109.3 pg/ml and TNF-α 3.8 pg/ml. In uncomplicated MI peak IL-1Ra levels were 1,088 pg/ml, IL-6 34.1 pg/ml and TNF-α 2.6 pg/ml. Conclusions: The inflammation-associated cytokines TNF-α, IL-6 and IL-1Ra are significantly elevated in patients with MI complicated by CS when compared to patients with uncomplicated MI. Among shock-patients IL-1Ra levels are promising diagnostic markers for early identification of patients developing SIRS, heralding a poor outcom

Metabolic link between phosphatidylethanolamine and triacylglycerol metabolism in the yeast Saccharomyces cerevisiae

In the yeast Saccharomyces cerevisiae triacylglycerols (TAG) are synthesized by the acyl-CoA dependent acyltransferases Dga1p, Are1p, Are2p and the acyl-CoA independent phospholipid:diacylglycerol acyltransferase (PDAT) Lro1p which uses phosphatidylethanolamine (PE) as a preferred acyl donor. In the present study we investigated a possible link between TAG and PE metabolism by analyzing the contribution of the four different PE biosynthetic pathways to TAG formation, namely de novo PE synthesis via Psd1p and Psd2p, the CDP-ethanolamine (CDP-Etn) pathway and lyso-PE acylation by Ale1p. In cells grown on the non-fermentable carbon source lactate supplemented with 5 mM ethanolamine (Etn) the CDP-Etn pathway contributed most to the cellular TAG level, whereas mutations in the other pathways displayed only minor effects. In cki1∆dpl1∆eki1∆ mutants bearing defects in the CDP-Etn pathway both the cellular and the microsomal levels of PE were markedly decreased, whereas in other mutants of PE biosynthetic routes depletion of this aminoglycerophospholipid was less pronounced in microsomes. This observation is important because Lro1p similar to the enzymes of the CDP-Etn pathway is a component of the ER. We conclude from these results that in cki1∆dpl1∆eki1∆ insufficient supply of PE to the PDAT Lro1p was a major reason for the strongly reduced TAG level. Moreover, we found that Lro1p activity was markedly decreased in cki1∆dpl1∆eki1∆, although transcription of LRO1 was not affected. Our findings imply that (i) TAG and PE syntheses in the yeast are tightly linked; and (ii) TAG formation by the PDAT Lro1p strongly depends on PE synthesis through the CDP-Etn pathway. Moreover, it is very likely that local availability of PE in microsomes is crucial for TAG synthesis through the Lro1p reaction