The Effects of High Mobility Group Box-1 Protein in Human Vascular Smooth Muscle Progenitor Cells in Regard to the Occurrence of Allograft Vasculopathy after Heart Transplantation

Immune system originally protects the body from infection of microorganisms. However, after the heart transplant surgery was performed, the donor's heart may induce the immune responses in the body of the recipient, which process is known as transplant rejection. Since the 1980s, cyclosporine, an efficient anti-rejection drugs was promoted, which greatly increased the survival rate of patients after heart transplantation and brought the medicine of heart transplant into a new era. Even this, chronic rejection is still the major problem faced by transplantation. Each year more than 5,000 people received heart transplantation worldwide, but about 25% of patients was death resulting in chronic rejection-related allograft vsculopathy after surgery for five years, which is still unclear in the underlying mechanism involving in vasculopathy. The typical characteristics of allograft vasculopathy after heart transplantation are coronary arteries endothelium damage (death of endothelial cells) and vascular intimal hyperplasia (proliferation of vascular smooth muscle cells). Previous pathological studies had demonstrated that vascular smooth muscle cells deposited on vasculopathy intima were mostly from the recipient. It is well known that bone marrow, circulating blood, arterial adventitia and skeletal muscle contain vascular smooth muscle progenitor cells (VSMPCs), therefore scientists have speculated that it may have considerable relevance exists between VSMPCs and allograft vasculopathy. High-mobility group protein B1 (HMGB1) is widely distributed in the lymphoid tissue, brain, liver, lung, heart, spleen, and kidney. Overexpression of HMGB1 has significant roles in tumor progression and tumor metastasis. Recently reports showed that HMGB1 is the intrinsic signal in rejection, it may star and regulate the immune responses, promote the maturation of immune cells, and induce the release of cytokines. The severity of allograft vasculopathy may also be associated with the plasma level of HMGB1. Although scientists considered that one of the causes of vasculopathy may come from the proliferation of VSMPCs, the real machines has rarely been reported and proved. Therefore, our group is very concern the effects of HMGB1 on VSMPCs function in heart transplant patients. In this project, we plan to employ cell and animal experiments to investigate the influence of HMBG1 on VSMPCs function and the occurrence of allograft vasculopathy on Rats. Futuremore, we expect to analysis the plasma level of HMGB1 and circulating VSMPCs in patients who underwent heart transplantation. Finally, we are going to analysis the clinical relevance between HMGB1, VSMPCs, and patients’ situation of vasculopathy using retrospective methods. We expect that the results of present study may provide insights into the development of therapeutic strategies for the prevention of chronic rejection and allograft vasculopathy after heart transplantation.