(2); however, the precise effects of CETP on atherogenesis are controversial. In humans, increased incidence of coronary heart disease has been associated with both CETP deficiency (3) and augmentation (4). In several animal models of atherosclerosis, the effects of CETP on vascular health are clearly dependent upon the metabolic context (5-11).Various researchers are attempting to target CETP as a form of therapy (9-13), but these approaches will be useless unless the circumstances where CETP acts as pro-or anti-atherogenic are properly clarified.Deficiency in endogenous estrogen accounts for the loss of protection against coronary heart disease after menopause or following bilateral ovariectomy (14). Estrogen deficiency per se does not alter plasma CETP activity as shown in castrated CETP transgenic mice (15). Also, estrogen therapy has no impact on the plasma CETP activity in humans (16) as well as in apolipoprotein B/CETP double transgenic mouse model (17).The present study aimed at investigating whether CETP expression would alter the development of atherosclerosis in a moderately hypercholesterolemic mouse model lacking ovarian hormones. For this purpose, mice expressing the human CETP gene were crossbred with LDL receptor (LDLR) knockout mice. On a high fat diet, the LDLR knockout mice develop extensive aorta atherosclerosis in a pattern similar to humans (18,19). We have shown here that the expression of the CETP gene significantly reduced the development of atherosclerotic lesions in ovariectomized hypercholesterolemic mice. Furthermore, this antiatherogenic effect of CETP was blunted by the estrogen replacement therapy.

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Several studies support the hypothesis that chronic diseases in adulthood might be triggered by events that occur during fetal development. This study examined the consequences of perinatal salt intake on blood pressure (BP) and carbohydrate and lipid metabolism in adult offspring of dams on high-salt [HSD; 8% (HSD2) or 4% (HSD1)], normal-salt (NSD; 1.3%), or low-salt (LSD; 0.15% NaCl) diet during pregnancy and lactation. At 12 wk of age, female Wistar rats were matched with adult male rats that were fed NSD. Weekly tail-cuff BP measurements were performed before, during, and after pregnancy. After weaning, the offspring received only NSD and were housed in metabolic cages for 24-h urine collection for sodium and potassium and nitrate and nitrite excretion measurements. At 12 wk of age, intra-arterial mean BP was measured, a euglycemic-hyperinsulinemic clamp was performed, and plasma lipids and nitrate and nitrite concentrations were determined. Tail-cuff BP was higher during pregnancy in HSD2 and HSD1 than in NSD and LSD dams. Mean BP (mm Hg) was also higher in the offspring of HSD2 (110 Ϯ 5) and HSD1 (107 Ϯ 5) compared with NSD (100 Ϯ 2) and LSD (92 Ϯ 2). Lower glucose uptake and higher plasma cholesterol and triacylglycerols were observed in male offspring from LSD dams (glucose uptake: HSD2 17 Ϯ 4, HSD1 15 Ϯ 3, NSD 11 Ϯ 3, LSD 4 Ϯ 1 mg · kg Ϫ1 · min Ϫ1 ; cholesterol: HSD2 62 Ϯ 6, HSD1 82 Ϯ 11, NSD 68 Ϯ 10, LSD 98 Ϯ 17 mg/dL; triacylglycerols: HSD2 47 Ϯ 15, HSD1 49 Ϯ 12, NSD 56 Ϯ 19, LSD 83 Ϯ 11 mg/dL). In conclusion, maternal salt intake during pregnancy and lactation has long-term influences on arterial pressure, insulin sensitivity, and plasma lipids of the adult offspring. (Pediatr Res 56: 842-848, 2004) Abbreviations BP, blood pressure HSD, high-salt diet HR, heart rate LSD, low-salt diet MBP, mean blood pressure NSD, normal-salt diet NOx, nitrate plus nitrite RAS, renin-angiotensin system tcBP, tail-cuff blood pressure Almost two decades ago, Barker and Osmond (1) proposed that ischemic heart disease could be triggered by events that occur during fetal life and early childhood (1). They showed an association between poor living standard during the perinatal period and ischemic heart disease in adulthood. This lifestyle possibly goes along with intrauterine growth retardation. Despite criticisms about the validity of their observations (2), the association between low birth weight and adult diseases is now further supported by several studies with similar findings (3-6). Moreover, the understanding of the mechanisms of this association represents a challenge for investigators in this area.Intrauterine growth is controlled by a complex interplay of maternal and fetal factors, including circulatory, endocrine, and metabolic systems (7). An increasing number of studies have shown that small modifications in fetal growth may have profound consequences in later life (8 -10).

We analyzed the effect of a 6-week aerobic exercise training program on the in vivo macrophage reverse cholesterol transport (RCT) in human cholesteryl ester transfer protein (CETP) transgenic (CETP-tg) mice. Male CETP-tg mice were randomly assigned to a sedentary group or a carefully supervised exercise training group (treadmill 15 m/min, 30 min sessions, five sessions per week). The levels of plasma lipids were determined by enzymatic methods, and the lipoprotein profile was determined by fast protein liquid chromatography (FPLC). CETP activity was determined by measuring the transfer rate of ¹⁴C-cholesterol from HDL to apo-B containing lipoproteins, using plasma from CETP-tg mice as a source of CETP. The reverse cholesterol transport was determined in vivo by measuring the [³H]-cholesterol recovery in plasma and feces (24 and 48 h) and in the liver (48 h) following a peritoneal injection of [³H]-cholesterol labeled J774-macrophages into both sedentary and exercise trained mice. The protein levels of liver receptors were determined by immunoblot, and the mRNA levels for liver enzymes were measured using RT-PCR. Exercise training did not significantly affect the levels of plasma lipids or CETP activity. The HDL fraction assessed by FPLC was higher in exercise-trained compared to sedentary mice. In comparison to the sedentary group, a greater recovery of [³H]-cholesterol from the injected macrophages was found in the plasma, liver and feces of exercise-trained animals. The latter occurred even with a reduction in the liver CYP7A1 mRNA level in exercised trained animals. Exercise training increased the liver LDL receptor and ABCA-1 protein levels, although the SR-BI protein content was unchanged. The RCT benefit in CETP-tg mice elicited by exercise training helps to elucidate the role of exercise in the prevention of atherosclerosis in humans.

MCT prevents the risk of pancreatitis due to postprandial hypertriglyceridemia but has the inconvenience of raising total cholesterol concentrations in primary hypertriglyceridemic subjects.