Role of angiotensin receptor-neprilysin inhibitor in diabetic complications.

Diabetes mellitus is a prevalent disorder with multi-system manifestations, causing a significant burden in terms of disability and deaths globally. Angio-tensin receptor-neprilysin inhibitor (ARNI) belongs to a class of medications for treating heart failure, with the benefits of reducing hospitalization rates and mortality. This review mainly focuses on the clinical and basic investigations related to ARNI and diabetic complications, discussing possible physiological and molecular mechanisms, with insights for future applications.

Advanced glycation end products impair coronary artery BK channels via AMPK/Akt/FBXO32 signaling pathway.

Background: Advanced glycation end products (AGEs) impair vascular physiology in Diabetes mellitus (DM). However, the underlying mechanisms remain unclear. Vascular large conductance calcium-activated potassium (BK) channels play important roles in coronary arterial function.Purpose: Our study aimed to investigate the regulatory role of AGEs in BK channels.Research Design: Using gavage of vehicle (V, normal saline) or aminoguanidine (A) for 8 weeks, normal and diabetic rats were divided into four groups: C+V group, DM+V group, C+A group, and DM+A group.Study Sample: Coronary arteries from different groups of rats and human coronary smooth muscle cells were used in this study.Data Collection and Analysis: Data were presented as mean ± SEM (standard error of mean). Student's t-test was used to compare data between two groups. One-way ANOVA with post-hoc LSD analysis was used to compare data between multiple groups.Results: Compared to the C+V group, vascular contraction induced by iberiotoxin (IBTX), a BK channel inhibitor, was impaired, and BK channel densities decreased in the DM+V group. However, aminoguanidine administration reduced the impairment. Protein expression of BK-ß1, phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK), and protein kinase B (PKB or Akt) were down-regulated, while F-box protein 32 (FBXO32) expression increased in the DM+V group and in high glucose (HG) cultured human coronary smooth muscle cells. Treatment with aminoguanidine in vitro and in vivo could reverse the above protein expression. The effect of aminoguanidine on the improvement of BK channel function by inhibiting the generation of AGEs was reversed by adding MK2206 (Akt inhibitor) or Compound C (AMPK inhibitor) in HG conditions in vitro.Conclusions: AGEs aggravate BK channel dysfunction via the AMPK/Akt/FBXO32 signaling pathway.

Acute renal injury after thoracic endovascular aortic repair of Stanford type B aortic dissection: incidence, risk factors, and prognosis.

BACKGROUND/PURPOSE: Acute kidney injury (AKI) significantly increases the risk of mortality in patients following cardiovascular intervention procedures. This study was carried out to investigate the incidence, predictors, and prognostic implications of AKI after thoracic endovascular aortic repair (TEVAR) of Stanford type B aortic dissection. METHODS: A total of 156 patients with Stanford type B aortic dissection who underwent TEVAR were retrospectively analyzed between February 1, 2004 and October 31, 2011. Multivariable regression was used to predict risk factors for AKI. Association between baseline characteristics, postoperative AKI, and mortality during follow up was evaluated. RESULTS: AKI was identified in 48 (30.8%) of 156 patients, with seven (14.5%) patients requiring continuous renal replacement therapy. The in-hospital mortality rate was 0% in patients without AKI and 12.5% in those with AKI (p = 0.001). Univariate analysis identified preoperative chronic kidney disease, acute dissection, complicated dissection, malperfusion complications with comprehensive complications, and postoperative minimum estimated glomerular filtration rate within 48 hours as associated with AKI. Malperfusion complications [odds ratio (OR) = 4.828; 95% confidence interval (CI) = 1.163-20.03] were the only independent predictor of AKI. Patients suffering from AKI had a 14-fold increased risk for 30-day mortality (OR = 14.3; 95% CI = 1.7-118.4; p = 0.014) and a 10-fold increased risk for 1-year mortality (OR = 9.5; 95% CI = 2.02-44.9; p = 0.004). CONCLUSION: A significant rate of AKI was observed following TEVAR and was associated with an increase in 30-day and 1-year mortality. Malperfusion complications were identified as an independent predictor of AKI.