Effects of atorvastatin on fasting and postprandial complement component 3 response in familial combined hyperlipidemia

Abstract

The diagnosis is based on clinical criteria such as the presence of "multiple-type hyperlipidemia," increased plasma apolipoprotein B (apoB), and a positive family history of premature coronary heart disease (CHD) (1-10). Abdominal obesity and increased body mass index (BMI) have been identified as independent factors for the development of hyperlipidemia and CHD in FCHL (4,8,(10)(11)(12). Associations with the complement system have also been reported (13,14). The genetic basis of FCHL has not been elucidated, although several groups have provided evidence suggesting that different genes are involved in the pathogenesis of this disorder (15-23).Impaired FFA metabolism in the postprandial as well as in the postabsorptive period is closely related to the expression of the FCHL phenotype (24-28). FCHL patients have increased postprandial FFA concentrations, compared with healthy controls (24,26,27). Increased postprandial FFA concentrations result in an increased postprandial hepatic FFA flux, which could explain in part the well-known VLDL overproduction in FCHL (26). More recently, an impaired postprandial complement component 3 (C3) response has been associated with the disturbed postprandial FFA handling (27).In vitro and in vivo experiments have demonstrated that the uptake of FFA by peripheral cells is stimulated by acylation-stimulating protein (ASP) (29, 30), which is one of the immunologically inactive cleavage products of C3 (30). Different studies in FCHL and non-FCHL subjects have shown a strong correlation between fasting C3 concentrations and fasting lipid parameters, especially plasma triglycerides (TGs) (13,14,27,31,32). Furthermore, C3 is a powerful indicator for the risk of myocardial infarction in men (32), and recently, it has been shown that C3 depositions are found predominantly in ruptured atherosclerotic plaques in humans (33), suggesting a pathogenetic involvement in the process of atherosclerosis and acute coronary syndromes. Moreover, both fasting and post-

Human plasma complement C3 is independently associated with coronary heart disease, but only in heavy smokers (the CODAM study)

“…The association between C3 and CHD in the group of never & light smokers was and remained non-significant and very modest, if present at all ( Table 2, models 1-6). There are indications in the literature that statin therapy might reduce plasma levels of complement C3 [23][24][25] and since a substantial number of subjects in our study received statin therapy (42% of the subjects with CHD, 11% of those without) this might to …”

A single early postnatal estradiol injection affects morphology and gene expression of the ovary and parametrial adipose tissue in adult female rats

“…Moreover, chylomicrons are the strongest stimulators of adipocyte C3 production via activation of the alternative complement cascade [74]. A postprandial C3 increment was observed in healthy subjects, in patients with coronary artery disease, and in patients with familial combined hyperlipidemia [75].…”

Complement component 3 polymorphisms interact with polyunsaturated fatty acids to modulate risk of metabolic syndrome

“…Fasting and postprandial triacylglycerol metabolism is disturbed in MetS (24). The postprandial C3 increment is related to triacylglycerol and NEFA metabolism (6), and chylomicrons are the strongest stimulators of adipocyte C3 production (25). It is not known whether plasma fatty acid composition directly influences C3 activation.…”