MicroRNA-122-5p promotes renal fibrosis and injury in spontaneously hypertensive rats by targeting FOXO3.

Hypertensive renal injury is accompanied by tubular interstitial fibrosis leading to increased risk for renal failure. This study aimed to explore the influences of miR-122-5p in hypertension-mediated renal fibrosis and damage. 14-week-old male SHR and WKY rats were randomly assigned to treat with rAAV-miR-122-5p or rAAV-GFP for 8 weeks. There were marked increases in miR-122-5p and Kim-1 levels and decreases in FOXO3 and SIRT6 levels in hypertensive rats. Transfection with rAAV-miR-122-5p triggered exacerbation of renal fibrosis, apoptosis and inflammatory injury in SHR, associated with downregulated levels of FOXO3, SIRT6, ATG5 and BNIP3 as well as upregulated expression of Kim-1, NOX4, CTGF, and TGF-ß1. In cultured primary mouse renal tubular interstitial fibroblasts, exposure to angiotensin II resulted in obvious downregulation of FOXO3, SIRT6, ATG5, BNIP3 and nitric oxide levels as well as augmented cellular migration, oxidative stress, and inflammation, which were exacerbated by miR-122-5p mimic while rescued by miR-122-5p inhibitor and rhFOXO3, respectively. Notably, knockdown of FOXO3 strikingly blunted cellular protective effects of miR-122-5p inhibitor. In summary, miR-122-5p augments renal fibrosis, inflammatory and oxidant injury in hypertensive rats by suppressing the expression of FOXO3. Pharmacological inhibition of miR-122-5p has potential therapeutic significance for hypertensive renal injury and fibrosis-related kidney diseases.

Healthcare quality and mortality among patients hospitalized for heart failure by hospital level in Beijing, China.

AIMS: This study sought to compare healthcare quality and 30 day, 90 day, and 1 year mortality rates among patients admitted to secondary and tertiary hospitals for heart failure (HF) in Beijing. METHODS AND RESULTS: This study retrospectively enrolled patients hospitalized with a primary discharge diagnosis of HF during January 2014 to December 2015, from five tertiary and four secondary hospitals, in Beijing, China. Mortality data were extracted from Beijing Death Surveillance Database. HF healthcare quality indices were used to evaluate in-hospital care. Associations between hospital level and mortality rates were assessed using generalized linear mixed models, adjusting for patients' baseline characteristics and intra-hospital correlation. Data from 1413 patients (median [interquartile range] age = 74 [65-80] years, 52.7% female) from secondary hospitals and 1250 patients (median [interquartile range] age = 72 [61-79] years, 43.3% female) from tertiary hospitals were collected. Rates of left ventricular ejection fraction assessment (73.2% vs. 90.1%) and combined use of ß-blockers and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (30.1% vs. 49.3%) were lower in secondary hospitals than those in tertiary hospitals, respectively. Patients admitted to secondary hospitals had a higher 90 day mortality [10.8% vs. 5.0%; adjusted odds ratio (OR): 2.06; 95% confidence interval (CI): 1.10-3.84, P = 0.024 and a higher 1 year mortality rate [21.0% vs. 12.1%; adjusted OR: 1.64; 95% CI: 1.02-2.62, P = 0.039], but 30 day mortality rates were not significantly different (5.5% vs. 3.0%; adjusted OR: 1.49; 95% CI: 0.63-3.52, P = 0.368). CONCLUSIONS: Worse quality of care for patients with HF in secondary hospitals was associated with higher 90 day and 1 year mortality rates. Improving care quality in secondary hospitals is crucial to improve prognosis of patients they served.

Catheter ablation for atrial fibrillation is associated with reduced risk of mortality in the elderly: a prospective cohort study and propensity score analysis.

BACKGROUND: It is unclear whether catheter ablation (CA) for atrial fibrillation (AF) affects the long-term prognosis in the elderly. This study aims to evaluate the relationship between CA and long-term outcomes in elderly patients with AF. METHODS: Patients more than 75 years old with non-valvular AF were prospectively enrolled between August 2011 and December 2017 in the Chinese Atrial Fibrillation Registry Study. Participants who underwent CA at baseline were propensity score matched (1:1) with those who did not receive CA. The outcome events included all-cause mortality, cardiovascular mortality, stroke/transient ischemic attack (TIA), and cardiovascular hospitalization. RESULTS: Overall, this cohort included 571 ablated patients and 571 non-ablated patients with similar characteristics on 18 dimensions. During a mean follow-up of 39.75 ± 19.98 months (minimum six months), 24 patients died in the ablation group, compared with 60 deaths in the non-ablation group [hazard ratio (HR) = 0.49, 95% confidence interval (CI): 0.30-0.79, P = 0.0024]. Besides, 6 ablated and 29 non-ablated subjects died of cardiovascular disease (HR = 0.25, 95% CI: 0.11-0.61, P = 0.0022). A total of 27 ablated and 40 non-ablated patients suffered stroke/TIA (HR = 0.79, 95% CI: 0.48-1.28, P = 0.3431). In addition, 140 ablated and 194 non-ablated participants suffered cardiovascular hospitalization (HR = 0.84, 95% CI: 0.67-1.04, P = 0.1084). Subgroup analyses according to gender, type of AF, time since onset of AF, and anticoagulants exposure in initiation did not show significant heterogeneity. CONCLUSIONS: In elderly patients with AF, CA may be associated with a lower incidence of all-cause and cardiovascular mortality.