BACKGROUND: We examined the effects of two doses of statins on liver regeneration through angiogenesis and its possible relation to acute phase responses. MATERIALS AND METHODS: Seventy-two rats were randomly divided into three groups: controls; low-dose atorvastatin (0.5 mg/kg/d); high-dose atorvastatin (2.5 mg/kg/d). Statin was administered daily by oral gavage for 7 days. After atorvastatin treatment, all animals in the three groups underwent 70% hepatectomy. Thereafter animals were subdivided into three subgroups, to evaluate the characteristics of liver regeneration proliferating cell nuclear antigen (PCNA), angiogenesis (KDR/Flk-1 [vascular endothelial growth factor-2]) and acute phase response (serum interleukin [IL]-6) at 12, 24, and 72 hours. RESULTS: At the 24 hours posthepatectomy, low-dose compared with high-dose atorvastatin increased liver regeneration (P = .004) and angiogenic responses compared also to controls (P = .026 and P = .059). However, there appeared no difference in IL-6 expression (P = .159). At the 72 hours posthepatectomy, low-dose atorvastatin treatment increased liver regeneration compared with controls (P = .047), but it showed no significant difference from the high-dose treatment (P = .109). Low doses of statin increased angiogenic responses compared with both control and high-dose animals (P = .016 and P = .002). Moreover, the high-dose group displayed decreased angiogenic responses compared with the control group (P = .044). Serum IL-6 expression was significantly greater among both low- and high-dose groups compared with controls (P = .005 and P = .003, respectively). CONCLUSIONS: Low-dose statin treatment increased KDR/Flk-1-dependent angiogenesis, which resulted in an increased regeneration response. In contrast, high-dose statin therapy decreased angiogenesis without affecting long-term regeneration responses. Finally, statin therapy may contribute to liver regeneration due to prolonged IL-6 expression independent of statin doses.
BACKGROUND: We examined the effects of two doses of statins on liver regeneration through angiogenesis and its possible relation to acute phase responses. MATERIALS AND METHODS: Seventy-two rats were randomly divided into three groups: controls; low-dose atorvastatin (0.5 mg/kg/d); high-dose atorvastatin (2.5 mg/kg/d). Statin was administered daily by oral gavage for 7 days. After atorvastatin treatment, all animals in the three groups underwent 70% hepatectomy. Thereafter animals were subdivided into three subgroups, to evaluate the characteristics of liver regeneration proliferating cell nuclear antigen (PCNA), angiogenesis (KDR/Flk-1 [vascular endothelial growth factor-2]) and acute phase response (serum interleukin [IL]-6) at 12, 24, and 72 hours. RESULTS: At the 24 hours posthepatectomy, low-dose compared with high-dose atorvastatin increased liver regeneration (P = .004) and angiogenic responses compared also to controls (P = .026 and P = .059). However, there appeared no difference in IL-6 expression (P = .159). At the 72 hours posthepatectomy, low-dose atorvastatin treatment increased liver regeneration compared with controls (P = .047), but it showed no significant difference from the high-dose treatment (P = .109). Low doses of statin increased angiogenic responses compared with both control and high-dose animals (P = .016 and P = .002). Moreover, the high-dose group displayed decreased angiogenic responses compared with the control group (P = .044). Serum IL-6 expression was significantly greater among both low- and high-dose groups compared with controls (P = .005 and P = .003, respectively). CONCLUSIONS: Low-dose statin treatment increased KDR/Flk-1-dependent angiogenesis, which resulted in an increased regeneration response. In contrast, high-dose statin therapy decreased angiogenesis without affecting long-term regeneration responses. Finally, statin therapy may contribute to liver regeneration due to prolonged IL-6 expression independent of statin doses.
Authors: B V M Dasari; A Pathanki; J Hodson; K J Roberts; R Marudanayagam; D F Mirza; J Isaac; R P Sutcliffe; P Muiesan Journal: BJS Open Date: 2019-03-12