Abstract
BackgroundInflammation and endothelial dysfunction is implicated in the atherosclerosis initiation and progression in the setting of hyperlipidemia. Colchicine is a potent anti-inflammatory agent and whether colchicine combined with atorvastatin has synergistic effects on inflammation amelioration and endothelial function improvement is unknown.MethodsHyperlipidemic rat model was produced by high-fat and high-cholesterol diet for 6 weeks. Rats with normal diet were served as shame group. In hyperlipidemic group, normal saline, atorvastatin (10 mg/kg body weight/day), colchicines (0.5 mg/kg body weight/day), or atorvastatin combined with colchicines (same dosages) were prescribed for 2 weeks. Serum levels of lipid profile, C-reactive protein (CRP), liver enzyme, lipoprotein associated phospholipase A2 (Lp-PLA2) and nitric oxide (NO) production were serially assessed.ResultsBefore the beginning of the study, all laboratory variables were comparable among each group. After 6 weeks of hyperlipidemic model production, serum levels of cholesterols, CRP and Lp-PLA2 were significantly increased when compared to sham group, whereas NO production was reduced. With 2 weeks of colchicine therapy, serum levels of CRP and Lp-PLA2 were decreased and NO production was enhanced in the colchicine group in a lipid-lowering independent manner. Added colchicine into atorvastatin therapy further improved NO production and decreased CRP and Lp-PLA2 levels, indicating a potential synergism of colchicine and atorvastatin.ConclusionColchicine combined with atorvastatin may have stronger protective effects on improving endothelial function and ameliorating inflammation in rats with hyperlipidemia.
Highlights
Hyperlipidemia is a major cause of multiple diseases such as atherosclerotic cardiovascular diseases (CVD) [1,2]
Thereafter, a large number of clinical and experimental studies have consistently revealed that increased lipoprotein associated phospholipase A2 (Lp-PLA2) level was associated with increased risk of cardiovascular events [13,14,15], which was considered to be associated with the increased production of lyso-phosphotidylcholine (Lyso-PC) and oxidized non-esterified fatty acids, two potent proinflammatory and pro-atherosclerotic intermediates derived from ox-LDL degradation by Lp-PLA2 [16,17]
Serum level of C-reactive protein (CRP) was profoundly increased in hyperlipidemic model groups, indicating that hyperlipidemia was significantly associated with systemic inflammation
Summary
Hyperlipidemia is a major cause of multiple diseases such as atherosclerotic cardiovascular diseases (CVD) [1,2]. The mechanisms of hyperlipidemia implicated in the initiation and progression of CVD predominantly involve sustained endothelial dysfunction and vascular inflammation [3,4,5]. Some basic studies showed that Lp-PLA2 was beneficial for deterring atherosclerosis progression by means of degrading PAF, a potent pro-inflammatory cytokine [10,11,12]. Thereafter, a large number of clinical and experimental studies have consistently revealed that increased Lp-PLA2 level was associated with increased risk of cardiovascular events [13,14,15], which was considered to be associated with the increased production of lyso-phosphotidylcholine (Lyso-PC) and oxidized non-esterified fatty acids (oxNEFAs), two potent proinflammatory and pro-atherosclerotic intermediates derived from ox-LDL degradation by Lp-PLA2 [16,17]. Colchicine is a potent anti-inflammatory agent and whether colchicine combined with atorvastatin has synergistic effects on inflammation amelioration and endothelial function improvement is unknown
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