The mevalonate pathway is essential for cholesterol biosynthesis. Previous studies have suggested that the key enzyme in this pathway, farnesyl diphosphate synthase (FDPS), regulates the cardiovascular system. We used human samples and mice that were deficient in cardiac FDPS (c-Fdps À/À mice) to investigate the role of FDPS in cardiac homeostasis. Cardiac function was assessed using echocardiography. Left ventricles were examined and tested for histological and molecular markers of cardiac remodeling. Our results showed that FDPS levels were downregulated in samples from patients with cardiomyopathy. Furthermore, c-Fdps À/À mice exhibited cardiac remodeling and dysfunction. This dysfunction was associated with abnormal activation of Ras and Rheb, which may be due to the accumulation of geranyl pyrophosphate. Activation of Ras and Rheb stimulated downstream mTOR and ERK pathways. Moreover, administration of farnesyltransferase inhibitors attenuated cardiac remodeling and dysfunction in c-Fdps À/À mice. These results indicate that FDPS plays an important role in cardiac homeostasis. Deletion of FDPS stimulates the downstream mTOR and ERK signaling pathways, resulting in cardiac remodeling and dysfunction.
Ventricular arrhythmias (VTA) usually occur following acute myocardial infarction (AMI). However, risk factors for VTA attack after AMI have been not well-recognized. The purpose of the study is to identify risk factors associated with the incidence of VTA complicating AMI. A total of 200 patients with AMI who were admitted to our hospital from February 2018 to February 2020 were retrospectively analyzed. These 200 patients were classified into a non-VTA group ( n = 140 ) and a VTA group ( n = 60 ) based on the occurrence of VTA within 24 after AMI. Patients in the VTA group were older than those in the non-VTA group. The VTA group had more numbers of WBCs and neutrophils than the non-VTA group. The level of serum potassium was lower, but the levels of cTnT and CK-MB were higher in the VTA group than in the non-VTA group. The VTA group presented an increase in proportions of anterior MI, TpTe, and proportions of Killip classification ≥ class II but a decline in LVEF when comparable to the non-VTA group. The two groups were not significantly different concerning other variables including sex, tobacco use, alcohol consumption, diabetes mellitus, hypertension, heart rate, Scr, SUA, BUN, PTL counts, TC, TG, HDL-C, LDL-C, D-dimer, BNP, LVS, LVP, and LVEDd. The levels of hsCRP, endothelin-1, and TNF-α were remarkably higher in the VTA group than in the non-VTA group ( P < 0.001 ). Multivariate logistic regression analysis was performed, with clinical variables including age, WBCs, neutrophils, serum potassium, cTnT, CK-MB, hsCRP, endothelin-1, TNF-α, anterior MI, TpTe, proportions of Killip classification ≥ class II, and LVEF as an independent variable and with the occurrence of VTA as a dependent variable. It was revealed that serum potassium, cTnT, CK-MB, hsCRP, endothelin-1, TpTe, proportions of Killip classification ≥ class II, and LVEF were independent risk factors of VTA complicating AMI. Compared with the non-VTA group, the incidence rate of simple left heart failure, total heart failure, stroke, and dyslipidemia in the VTA group was significantly higher than those in the non-VTA group ( P < 0.05 ). It was found that the proportion of all-cause deaths within one year outside the hospital was higher in the VAT group than in the non-VAT group ( P < 0.05 ). Collectively, the study demonstrates serum potassium, cTnT, CK-MB, hsCRP, endothelin-1, TpTe, proportions of Killip classification ≥ class II, and LVEF were independent risk factors of VTA complicating AMI.
Background: Association between plasma pentraxin-3 (PTX-3) and clinical outcomes in patients with coronary artery disease (CAD) remains not fully determined. An updated meta-analysis of cohort studies was performed to systematically evaluate the association.Methods: Cohort studies evaluating the association between plasma PTX-3 and adverse outcomes [mortality and major adverse cardiovascular events (MACEs)] in adults with CAD were identified by systematic search of PubMed, Embase, and Web of Science databases. Only studies with multivariate analysis were included. A random-effects model incorporating the potential intrastudy heterogeneity was used for the meta-analysis.Results: A total of 16 studies including 11,007 patients were included. Pooled results showed that patients with highest level of PTX-3 were independently associated with higher risk of mortality [adjusted risk ratio (RR): 2.09, 95% CI: 1.60 to 2.74, p < 0.001; I2 = 50%] and MACEs (adjusted RR: 1.80, 95% CI: 1.43 to 2.28, p < 0.001; I2 = 49%). Subgroup analyses showed that the associations between PTX-3 and poor prognosis in CAD were consistent in patients with ST-segment elevation myocardial infraction, non-ST-segment elevation acute coronary syndrome, and stable CAD (p < 0.05 for each subgroup). Besides, the association between PTX-3 and increased incidence of mortality and MACEs were consistent in short-term (within 1 year) and long-term (over 1 year) studies and in studies with or without adjustment of C-reactive protein (CRP) (p < 0.05 for each subgroup).Conclusion: Higher plasma PTX-3 is associated with poor prognosis in patients with CAD, which may be independent of the CAD subtype, follow-up durations, and adjustment of CRP.
Background The model for end-stage liver disease (MELD) score is a marker used to evaluate end-stage liver disease in patients with liver failure and is suggested to be valuable in evaluating heart diseases such as heart failure. Because patients with heart failure and myocardial infarction often use anticoagulants, there is an impact on the international normalized ratio (INR). Therefore, removing the INR from MELD score to form MELD-XI score may help to more accurately evaluate the cardiac function in patients with heart failure. This study was conducted to examine the predictive value of MELD-XI score in patients with acute myocardial infarction after coronary artery stenting, as there is a lack of literature in this area. Methods The data of 318 patients with acute myocardial infarction admitted to The People’s Hospital of Dazu from January 2018 to January 2021 was retrospectively collected. According to the MELD-XI score on admission, the patients were divided into a high-MELD-XI score group (n=159) and a low-MELD-XI score group (n=159). The patients were followed up for 1 year after surgery to observe the long-term prognosis and the long-term prognosis of the 2 groups was compared. Results Compared with that in the low-MELD-XI score group, the left ventricular ejection fraction in the high-MELD-XI score group was significantly reduced (51.61%±7.66% vs. 60.48%±5.94%; P<0.001), while the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) increased significantly (821.58±461.81 vs. 723.51±335.16 ng; P=0.031). The MELD-XI score had a certain predictive value for heart failure in patients with acute myocardial infarction after coronary artery stenting, and the area under the curve was 0.730 (95% CI: 0.670–0.791; P<0.001). The MELD-XI score had a predictive value for death in patients with acute myocardial infarction after coronary artery stenting, and the area under the curve was 0.704 (95% CI: 0.564–0.843; P=0.022). MELD-XI score was significantly negatively correlated with left ventricular ejection fraction in patients with acute myocardial infarction after coronary artery stenting (r=–0.444; P<0.001). Conclusions MELD-XI could evaluate the cardiac function of patients with acute myocardial infarction after coronary artery stenting, which was valuable in predicting the prognosis.
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