Pyrroloquinoline Quinone (PQQ) Improves Long-term Survival of Fat Grafts by Alleviating Oxidative Stress and Promoting Angiogenesis During the Early Phase After Transplantation.

Abstract

Reducing absorption after autologous fat grafting is a current challenge. Pyrroloquinoline quinone (PQQ) is the strongest known catalyst of redox reactions, which can scavenge reactive oxygen species (ROS) and alleviate oxidative stress. The aim of this study was to establish an in vivo model of PQQ-assisted lipotransfer and clarify the role of PQQ in reducing oxidative stress, alleviating apoptosis, and promoting angiogenesis during the acute hypoxic phase after grafting. In addition the study was performed to assess whether this intervention would have a positive effect on the improvement of long-term volume retention. Different concentrations of PQQ (low: 10 μM, medium: 100 μM, and high: 1000 μM) were mixed with human adipose tissue and transplanted subcutaneously into nude mice. Meanwhile, a control group of phosphate-buffered saline in an equal volume to PQQ was set up. On the third day after grafting, whole mount fluorescence staining was applied to detect ROS, mitochondrial membrane potential (MMP), apoptosis, adipocyte activity, and angiogenesis. Graft volume retention rate and electron microscopic morphology were evaluated at the third month. Immunohistochemistry and polymerase chain reaction (PCR) were further employed to elucidate the mechanism of action of PQQ. PQQ-assisted fat grafting improved the long-term volume retention, promoted the quality and viability of the adipose tissue, and reduced the level of fibrosis. The underlying mechanism of PQQ assisted in scavenging the accumulated ROS, restoring MMP, enhancing adipocyte viability, alleviating tissue apoptosis, and promoting timely angiogenesis during the hypoxia stress phase. The most effective concentration of PQQ was 100 μM. Immunohistochemistry and PCR experiments confirmed that PQQ reduced the expression of Bax and cytochrome c in the mitochondrial apoptotic pathway and increased the level of the antiapoptotic molecule Bcl-2. PQQ could improve the long-term survival of adipocytes by alleviating hypoxic stress and promoting timely angiogenesis in the early phase following lipotransfer.