Defective high‐density lipoprotein lipoprotection in type 2 diabetes during acute myocardial infarction is rescued by apolipoprotein M/sphingosine‐1‐phosphate loading

Abstract Aims Mortality of patients with type 2 diabetes (T2D) after acute myocardial infarction (AMI) is tremendous and massively increased compared to non‐T2D individuals. The reasons are unclear. High‐density lipoprotein (HDL) conducts lipoprotection during AMI, leading to improved outcomes. We hypothesised that T2D‐HDL lacks lipoprotective properties. Materials and Methods HDL was isolated from healthy, non‐T2D individuals and T2D patients. This human HDL was administered to mice undergoing AMI. Infarct size and cardiac function were assessed by histology and echocardiography. HDL composition was determined by mass spectrometry. Results HDL from healthy individuals but not from T2D patients reduced infarct size and improved cardiac function after AMI. Analysing HDL composition revealed lack of sphingosine‐1‐phosphate and Apolipoprotein M in T2D‐HDL. Ex‐vivo loading of HDL with these components rescued T2D‐HDL lipoprotection. Conclusions We revealed that T2D‐HDL lacks lipoprotection during AMI. This might be a reason for enhanced mortality of T2D patients after AMI. Furthermore, we found an option to rescue T2D‐HDL lipoprotection.