Tumor Necrosis Factor Receptor Superfamily Member 21 Induces Endothelial-Mesenchymal Transition in Coronary Artery Endothelium of Type 2 Diabetes Mellitus.
Po-Chao HsuJiun-Chi HuangWei-Chung TsaiWei-Wen HungWei-An ChangLing-Yu WuChao-Yuan ChangYi-Chun TsaiYa-Ling HsuPublished in: Biomedicines (2022)
Diabetes mellitus (DM) is an increasing threat to human health and regarded as an important public issue. Coronary artery disease is one of the main causes of death in type 2 DM patients. However, the effect of hyperglycemia on coronary artery endothelial cells (CAECs) and the pathophysiologic mechanisms are still not well-explored. This study aims to explore the signal pathway and novel biomarkers of injury of CAECs in DM in understanding the microenvironment changes and mechanisms of diabetic heart disease. Next-generation sequence (NGS) and bioinformatics analysis to analyze the CAECs of one type 2 DM patient and one normal individual was performed, and it was found that tumor necrosis factor receptor superfamily member 21 (TNFRSF21) was a soluble factor in circulating system. Further experiments confirmed that advanced glycation end products (AGEs), the metabolite derived by hyperglycemia, increased the expression of TNFRSF21 in CAECs. TNFRSF21 induced endothelial-mesenchymal transition (EndoMT) in CAECs, resulting in increased permeability of CAECs. In addition, levels of serum TNFRSF21 were higher in type 2 DM patients with left ventricular hypertrophy (LVH) than those without LVH. Serum TNFRSF21 levels were also positively correlated with the LV mass index and negatively with LV systolic function. Serum TNFRSF21 levels were associated with changes in cardiac structure and function in patients with type 2 DM. In conclusion, TNFRSF21 plays a pathogenic role in heart disease of type 2 DM, and can be used as a biomarker of the impairment of cardiac structure and function in type 2 DM patients.
Keyphrases
- left ventricular
- coronary artery
- endothelial cells
- glycemic control
- coronary artery disease
- end stage renal disease
- ejection fraction
- stem cells
- newly diagnosed
- heart failure
- human health
- chronic kidney disease
- type diabetes
- pulmonary artery
- blood pressure
- risk assessment
- bone marrow
- healthcare
- prognostic factors
- pulmonary hypertension
- emergency department
- acute myocardial infarction
- percutaneous coronary intervention
- cardiovascular disease
- diabetic rats
- oxidative stress
- poor prognosis
- metabolic syndrome
- adipose tissue
- pulmonary arterial hypertension
- skeletal muscle