Exercise modulates APOE expression in brain cortex of female APOE3 and APOE4 targeted replacement mice.

Apolipoprotein E (ApoE) is the main cholesterol carrier of the brain and the ε4 gene variant (APOE4) is the most prevalent genetic risk factor for Alzheimer's disease (AD), increasing risk up to 15-fold. Several studies indicate that APOE4 modulates critical factors for neuronal function, including brain-derived neurotrophic factor (BDNF) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α). Both proteins show exercise-induced upregulation, which is presumed to mediate many of the beneficial effects of physical activity including improved cognition; however, there is variability in results between individuals potentially in-part due to genetic variations including APOE isoform. This study aimed to determine if the two most prevalent human APOE isoforms influence adaptive responses to exercise-training. Targeted replacement mice, homozygous for either APOE3 or APOE4 were randomized into exercised and sedentary groups. Baseline locomotor function and voluntary wheel-running behavior was reduced in APOE4 mice. Exercised groups were subjected to daily treadmill running for 8 weeks. ApoE protein in brain cortex was significantly increased by exercise in both genotypes. PGC-1α mRNA levels in brain cortex were significantly lower in APOE4 mice, and only tended to increase with exercise in both genotypes. Hippocampal BDNF protein were similar between genotypes and was not significantly modulated by treadmill running. Behavioral and biochemical variations between APOE3 and APOE4 mice likely contribute to the differential risk for neurological and vascular diseases and the exercise-induced increase in ApoE levels suggests an added feature of the potential efficacy of physical activity as a preventative and therapeutic strategy for neurogenerative processes in both genotypes.

In-Hospital Outcomes of Coronary Artery Stenting in Patients With ST-Elevation Myocardial Infarction (STEMI) and Metabolic Syndrome: Insights From the National Inpatient Sample.

Background Metabolic syndrome (MetS) has been recognized as a global health problem. Concurrent MetS diagnosis in patients with ST-elevation myocardial infarction (STEMI) is becoming increasingly common. Given the paucity of studies on the impact of MetS on treatment outcomes in STEMI patients, the purpose of this study was to evaluate in-hospital mortality in STEMI patients with a concurrent MetS diagnosis undergoing a stenting procedure to treat their underlying coronary artery disease. Method Patients with or without MetS who underwent coronary stenting following STEMI between 2005 and 2014 were identified from the National Inpatient Sample database. Patients' demographics, comorbidities, and outcomes were compared using a t-test and Pearson's Chi-square test. In addition, 1:1 propensity score matching was performed for age, gender, and race. Results Out of 1,938,097 STEMI patients, 5,817 patients with MetS underwent coronary stenting following STEMI and were matched with 5,817 patients with no Mets. MetS group had significantly higher rates of diabetes, hypertension, hyperlipidemia, chronic kidney disease, and obstructive sleep apnea than the no MetS group but lower rates of heart failure and chronic obstructive pulmonary disease. In-hospital mortality following STEMI was significantly lower in patients with MetS (2.5% vs. 7.1%, p<0.001) and remained significant after adjusting for potential confounders (odds ratio (OR) 0.34, 95% confidence interval (95% CI) 0.28-0.42, p<0.0001). Conclusion Concurrent diagnosis of MetS among patients undergoing coronary stenting is associated with a decreased in-hospital mortality risk. The impact of specific MetS components on the observed reduction in mortality remains unclear and warrants evaluation in future studies.