Low cholesteryl ester transfer protein and phospholipid transfer protein activities are the factors making tree shrew and beijing duck resistant to atherosclerosis

Abstract

BackgroundTree shrew and beijing duck are regarded as animal models resistant to atherosclerosis (AS). This study was carried out to discover the potential mechanism.MethodsBlood samples were collected from healthy men and male animals. Plasma lipid profile and activities of cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) were measured, compared and analyzed in human, tree shrew, and Beijing duck.ResultsThe results showed that there were species differences on plasma lipid profile and activities of CETP and PLTP in the three species. Compared with human, tree shrew and beijing duck had higher high density lipoprotein cholesterol (HDL-C)/total cholesterol (TC) and HDL-C/low density lipoprotein cholesterol (LDL-C) ratios, but lower CETP and PLTP activities. In the three species, CETP and PLTP activities were negatively related with the ratio of HDL-C/LDL-C.ConclusionsThe present study suggested that low plasma CETP and PLTP activities may lead to a high HDL-C/LDL-C ratio and a high resistance to AS finally in tree shrew and beijing duck. Moreover, low PLTP activity may also make the animals resistant to AS by the relative high vitamin E content of apoB-containing lipoproteins and high anti-inflammatory and antioxidative properties of HDL particles. A detailed study in the future is recommended.

New promising potential in fighting atherosclerosis: HDL and reverse cholesterol transport

“…Animals that lack CETP, such as the rat and dog, have very high HDL. Other species that have large amounts of CETP, such as rabbits, monkeys and humans, have low HDL levels (13). Therefore, inhibiting CETP appears to be an effective means to raise HDL.…”

Structure and Function of Cholesteryl Ester Transfer Protein in the Tree Shrew

“…The RNA was reverse transcribed to the first strand cDNA using SuperScript TM First-Strand Synthesis System for RT-PCR. 1 lg of total RNA, 1 ll of 10 mM dNTP mix, 1 ll of oligo(dT) [12][13][14][15][16][17][18] (0.5 lg/ll), and some diethylpyrocarbonate (DEPC)-treated water were added into a tube to a final volume of 10 ll, mixed, and incubated at 65°C for 5 min, then cooled on ice for at least 1 min. In a separate tube, 2 ll of 109 RT buffer, 4 ll of 25 mM MgCl 2 , 2 ll of 0.1 M DTT, and 1 ll of RNaseOUT TM (40 U/ll) were added and mixed with the first mixture.…”

“…However, an increase in CETP activity decreases HDL-C, increases LDL-C, and finally increases atherosclerosis [10][11][12]. Recent comparative studies show that plasma CETP activity is significantly lower but the HDL-C/LDL-C ratio is higher in the tree shrew than in human and in the two species the CETP activities are negatively related with the HDL-C/LDL-C ratios, suggesting that the low CETP activity could lead to the high HDL-C level and resistance to AS in the tree shrew [13].…”

A lipidomics study reveals hepatic lipid signatures associating with deficiency of the LDL receptor in a rat model

“…Cholesteryl ester transfer protein (CETP) is an important factor in regulating lipoprotein metabolism, which transfers cholesterol ester (CE) from HDL to lipoproteins of lower density and is closely linked to atherosclerosis ( Masson et al, 2009 ; Quintao and Cazita, 2010 ). Some vertebrate species can be defined as two groups that have a distinct plasma lipoprotein profile and CETP activity ( Liu et al, 2010 , 1995 ; Tsutsumi et al, 2001 ). One group, including human, monkey, rabbit and hamster, has a low ratio of plasma HDL cholesterol (HDL-C) to total cholesterol (TC) and concomitant high CETP activity.…”

“…In contrast the other group, including mouse, rat, dog and tree shrew, displays a high HDL-C/TC ratio and concomitant low CETP activity. As a consequence, the first group is susceptible to atherosclerosis while the second group exhibits resistance to atherosclerosis ( Liu et al, 2010 , 1995 ; Tsutsumi et al, 2001 ). The plasma lipoprotein profile in mice and rats hampers their usage as animal models for the discovery of cholesterol-lowering drugs.…”