1.
Neutrophil extracellular traps: The core player in vascular complications of diabetes mellitus.
Berezin, A
Diabetes & metabolic syndrome. 2019;(5):3017-3023
Abstract
Diabetes mellitus (DM) is the most important metabolic disease with major threat for public health and increased risk of premature death. The prevalence of DM steadily rises in developing and developed countries achieving the epidemic level. Manifestation and progression of DM corresponds to developing vasculopathies, such as retinopathy, micro- and macro angiopathies, which negatively influence on clinical outcomes and quality-of-life. Although there are remarkable differences in the prevalence of vasculopathy in various types of DM, hyperglycemia and lipotoxicity are discussed as a major factors contributing to vascular complications partly through inducing neutrophil extracellular trap (NET). The NET or NETosis is unique form of cell death, which is an important core component of innate immune system. The review is dedicated the role of NET as a link between endothelium, inflammation and thrombosis that is crucial for development of DM-induced vasculopathy. It has suggested that NET formation could be not just a target for the DM care, but also a biomarker for stratification of DM patients at higher risk of vascular complications.
2.
Effect of selective BET protein inhibitor apabetalone on cardiovascular outcomes in patients with acute coronary syndrome and diabetes: Rationale, design, and baseline characteristics of the BETonMACE trial.
Ray, KK, Nicholls, SJ, Ginsberg, HD, Johansson, JO, Kalantar-Zadeh, K, Kulikowski, E, Toth, PP, Wong, N, Cummings, JL, Sweeney, M, et al
American heart journal. 2019;:72-83
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Abstract
After an acute coronary syndrome (ACS), patients with diabetes remain at high risk for additional cardiovascular events despite use of current therapies. Bromodomain and extra-terminal (BET) proteins are epigenetic modulators of inflammation, thrombogenesis, and lipoprotein metabolism implicated in atherothrombosis. The BETonMACE trial tests the hypothesis that treatment with apabetalone, a selective BET protein inhibitor, will improve cardiovascular outcomes in patients with diabetes after an ACS. DESIGN Patients (n = 2425) with ACS in the preceding 7 to 90 days, with type 2 diabetes and low HDL cholesterol (≤40 mg/dl for men, ≤45 mg/dl for women), receiving intensive or maximum-tolerated therapy with atorvastatin or rosuvastatin, were assigned in double-blind fashion to receive apabetalone 100 mg orally twice daily or matching placebo. Baseline characteristics include female sex (25%), myocardial infarction as index ACS event (74%), coronary revascularization for index ACS (80%), treatment with dual anti-platelet therapy (87%) and renin-angiotensin system inhibitors (91%), median LDL cholesterol 65 mg per deciliter, and median HbA1c 7.3%. The primary efficacy measure is time to first occurrence of cardiovascular death, non-fatal myocardial infarction, or stroke. Assumptions include a primary event rate of 7% per annum in the placebo group and median follow-up of 1.5 years. Patients will be followed until at least 250 primary endpoint events have occurred, providing 80% power to detect a 30% reduction in the primary endpoint with apabetalone. SUMMARY BETonMACE will determine whether the addition of the selective BET protein inhibitor apabetalone to contemporary standard of care for ACS reduces cardiovascular morbidity and mortality in patients with type 2 diabetes. Results are expected in 2019.