Background: Extreme obesity pathology is with a risk factor for heart failure (HF), whereas the obesity paradox in HF shows that obese subjects had a good prognosis. The mechanism underlying the obesity paradox in HF prognosis is unclear till now. We aimed to provide evidence for the molecular mechanisms of the obesity paradox in HF. Methods: Differentially expressed genes (DEGs) in ischemic HF samples were identified in the GSE57338 and GSE5406 datasets. Weighted gene co-expression network analysis (WGCNA) modules and a protein-protein interaction network (PPI) were constructed. HF-associated DEGs and pathways were screened in the Comparative Toxicogenomics Database (CTD). The expression of hub genes in adipose tissues from obese patients and LV samples from HF patients were validated in microarray datasets. Results: Three HF-associated WGCNA modules were identified and DEGs were associated with the ‘hsa04115: p53 signaling pathway’. SERPINE1 was the only common gene between DEGs and HF-associated genes in the CTD database. The SERPINE1 gene was downregulated in the white adipose tissues compared with brown adipose tissues (P = 3.90e-03) and was upregulated in the omental adipose tissues from obese patients compared with lean subjects (P = 3.85e-02). Conclusion: The downregulation of SERPINE1 expression might be responsible for the obesity paradox in HF via interacting with ESR1.

Background: The risk for unsuccessful reperfusion after streptokinase therapy may be caused by the antifibrinolytic effect of platelet-derived type 1 plasminogen activator inhibitor (PAI-1) and antistreptokinase antibodies. This study aims to show the relation of pretreatment PAI-1 levels of patients with acute myocardial infarction treated with streptokinase and the outcome of fibrinolysis, emphasizing on reperfusion with and without considering pretreatment antistreptokinase antibodies.Methods: Pretreatment PAI-1 and antistreptokinase antibodies levels of 61 patients with acute myocardial infarction, treated with streptokinase, were determined by an enzyme- linked immunosorbent assay kit method. Failure of thrombolysis with streptokinase was present when reperfusion was unsuccessful as assessed by noninvasive reperfusion criteria.Results: Mean pretreatment PAI-1 level of patients was 29.72±4.74 ng/ml. Thrombolysis with streptokinase failed significantly with higher pretreatment PAI-1 levels (p<0.05) in all patients and patients with negative pretreatment antistreptokinase antibodies.Conclusion: We showed that higher on reperfusion in patients with acute myocardial infarction, with and without considering pretreatment antistreptokinase pretreatment PAI-1 levels were associated with significant failure of streptokinase therapy with the emphasis antibodies (anti-SK). It seems that by estimating PAI-1>25 ng/1 and antistreptokinase antibodies higher than normal levels in patients before the start of streptokinase therapy, candidates for potentially unsuccessful streptokinase therapy (with failed reperfusion) can be identified in advance and an alternative therapy such as primary angioplasty with better immediate results can be started.