Diabetes concomitant to aortic stenosis is associated with increased expression of NF-κB and more pronounced valve calcification

• DOI: 10.1007/s00125-021-05545-w
• Publication Date: 2021-09-07T19:02:21Z
• Authors: Magdalena Kopytek; Piotr Mazur; Michał Ząbczyk; Anetta Undas; Joanna Natorska
• Keywords: Concomitant; Immunostaining

Abstract Aims/hypothesis Type 2 diabetes has been demonstrated to predispose aortic valve calcification. We investigated whether type concomitant stenosis (AS) enhances valvular inflammation and coagulation activation via upregulated expression of NF-κB, with subsequent increased bone morphogenetic protein (BMP-2). Methods In this case–control study, 50 individuals severe isolated AS were compared a control group 100 without diabetes. The median (IQR) duration since diagnosis was 11 (7–18) years, 36 (72%) had HbA 1c ≥48 mmol/mol (≥6.5%). Stenotic valves obtained during replacement surgery served for in loco BMP-2, prothrombin (FII) active factor X (FXa) immunostaining. vitro cultures interstitial cells (VICs), from used mechanistic experiments PCR investigations. Results Diabetic non-diabetic displayed enhanced FII FXa (all p ≤ 0.001). Moreover, the NF-κB BMP-2 positively correlated amounts FXa. Only diabetic participants, strongly associated serum levels , moderately fructosamine. Of importance, area (AVA) maximal transvalvular pressure gradient. conducted using VIC revealed that glucose (11 mmol/l) both ( < treated combination reactive oxygen species (ROS) inhibitor N -acetyl- l -cysteine), significantly suppressed. A comparable effect observed VICs cultured (BAY 11–7082), suggesting high doses activate oxidative stress leading proinflammatory actions VICs. Analysis mRNA confirmed these findings; caused 6.9-fold increase RELA (NF-κB p65 subunit), ROS reducing raised by 1.8- 3.2-fold, respectively. Conclusions/interpretation within stenotic leaflets. Increased is not only fructosamine but also AVA gradient, indicating strict long-term glycaemic needed patients This study suggests maintaining variables normal range may slow rate progression. Graphical abstract