Invited commentary
Apolipoproteins C-II and C-III and small dense low density lipoprotein: novel risk factors in metabolic syndrome?
Commentary on: Theodosios D. Filippatos et al. Small dense LDL cholesterol and apolipoproteins C-II and C-III in non-diabetic obese subjects with metabolic syndrome (Arch Med Sci 2008; 4, 3: 263–269)

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities, including dyslipidemia, abdominal obesity and elevated blood pressure levels [1]. MetS represents an important public health problem for 2 reasons. First, its prevalence is reaching epidemic proportions worldwide [1-6]. Second, most studies showed that MetS is associated with increased risk of developing type 2 diabetes mellitus (T2DM) and vascular disease [7, 8]. However, others argued that the presence of MetS does not confer more risk than the sum of its components [9]. One explanation for these discrepant findings may be that MetS is not a uniform condition [10]. Thus, some forms of MetS may carry a greater risk than others [10]. In this context, there is evidence that vascular risk rises as the number of diagnostic risk factors increases [1, 11]. Furthermore, patients with MetS might have additional vascular risk factors, including activation of pro-inflammatory and pro-thrombotic cascades [7, 12, 13], impaired renal function [14], as well as elevated uric acid levels [15]. Other potentially harmful lipid abnormalities may be present in MetS in addition to the diagnostic criteria of decreased high density lipoprotein cholesterol (HDL-C) and elevated triglyceride (TG) levels [1, 16]. These include elevated apolipoprotein (apo) C-II and C-III levels and a predominance of small dense low density lipoprotein cholesterol (sdLDL-C) [12, 16-18]. Apo C-II exerts a biphasic effect on lipoprotein lipase (LPL), the enzyme catabolizing TG-rich lipoproteins [19]. Physiologically, apo C-II activates LPL whereas elevated apo C-II levels inhibit LPL and might lead to hypertiglyceridemia [19]. Apo C-III inhibits LPL and down-regulates the catabolism of TGs [19, 20]. In turn, elevated TG levels not only might represent an independent vascular risk factor [21] but also predispose to an increased proportion of sdLDL particles [18]. Besides its role in TG regulation, apo C-II was identified in atherosclerotic lesions where it colocalizes with macrophages and forms amyloid fibrils [22]. The latter have been assigned pro-inflammatory properties and might be implicated in the pathogenesis of atherosclerosis [23]. Apo C-III also appears to exert pro-inflammatory actions and to induce endothelial dysfunction [20], the early stage in the pathogenesis of atherosclerosis [24]. Some studies showed that elevated apo C-II levels [25] and apo C-III [26, 27], as well as a predominance of sdLDL particles might be...


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