Increased NPC1L1 and serum cholesterol in a chronic rejection rat

Abstract

Increased NPC1L1 and serum cholesterol in a chronic rejection rat Abstract Purpose: To measure serum cholesterol and triglyceride levels and NPC1L1 mRNA and protein as an index of cholesterol absorption during the development of chronic rejection (CR) in a rat model of intestinal transplantation.Methods: Rats were randomly divided into two groups: Group 1 (n=20) underwent syngenic Lewis-to-Lewis transplantation and Group 2 (n=20) underwent allogenic F344-toLewis transplantation as well as treatment with FK506. Blood samples and intestinal tissue were procured on the 190th day a er operation. Histological changes were analyzed and the semiquantitative scores of histological parameters were compared. e serum levels of cholesterol and triglyceride were determined. e expression of Niemann-Pick C1 Like 1(NPC1L1) mRNA and protein were analyzed by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) and immunohistochemistry, respectively.Results: All the animals survived for the 190 days. e appearance and histology of isogra s were almost normal whereas the allogra s displayed thickened bowel wall and mesenteric brosis, concentric intimal thickening and interstitial brosis and in ammatory in ltration. e histology scores displayed a signi cant di erence between the allogra s and isogra s (P<0.001). No di erences were observed for triglycerides for the two groups.e serum cholesterol levels increased signi cantly in the allogenic group in comparison with the syngenic group (P=0.034), while no di erence was observed for triglyceride levels between groups. RT-PCR showed that the expression of NPC1L1 of allogra s increased signi cantly (P=0.004). Immunohistochemistry con rmed RT-PCR ndings.Conclusions: Neointima formation and mesenteric brosis were the dominant pathological features. e increased expression of NPC1L1 might contribute to hypercholesterolemia, which may be involved in the pathogenesis of transplant arteriosclerosis.ORIGINAL RESEARCH

Value of blood lipid in predicting graft dysfunction after organ and tissue transplantation: A study of Mendelian randomization

“…In fact, data shows that approximately 50% of heart transplant patients develop high levels of cholesterol and triglycerides within the first year of transplantation, and this proportion increases to 95% within 5 years ( www.nhlbi.nih.gov ). Moreover, hypercholesterolemia may play a role in the pathogenesis of allograft arteriosclerosis, further emphasizing the strong clinical correlation between altered lipid levels and allograft survival [ 28 ].…”