Dietary rose hip exerts antiatherosclerotic effects and increases nitric oxide-mediated dilation in ApoE-null mice.

Atherosclerosis is a disease in which atheromatous plaques develop inside arteries, leading to reduced or obstructed blood flow that in turn may cause stroke and heart attack. Rose hip is the fruit of plants of the genus Rosa, belonging to the Rosaceae family, and it is rich in antioxidants with high amounts of ascorbic acid and phenolic compounds. Several studies have shown that fruits, seeds and roots of these plants exert antidiabetic, antiobesity and cholesterol-lowering effects in rodents as well as humans. The aim of this study was to elucidate the mechanisms by which rose hip lowers plasma cholesterol and to evaluate its effects on atherosclerotic plaque formation. ApoE-null mice were fed either an HFD (CTR) or HFD with rose hip supplementation (RH) for 24 weeks. At the end of the study, we found that blood pressure and atherosclerotic plaques, together with oxidized LDL, total cholesterol and fibrinogen levels were markedly reduced in the RH group. Fecal cholesterol content, liver expression of Ldlr and selected reverse cholesterol transport (RCT) genes such as Abca1, Abcg1 and Scarb1 were significantly increased upon RH feeding. In the aorta, the scavenger receptor Cd36 and the proinflammatory Il1ß genes were markedly down-regulated compared to the CTR mice. Finally, we found that RH increased nitric oxide-mediated dilation of the caudal artery. Taken together, these results suggest that rose hip is a suitable dietary supplement for preventing atherosclerotic plaques formation by modulating systemic blood pressure and the expression of RCT and inflammatory genes.

Vascular smooth muscle cell proliferation depends on caveolin-1-regulated polyamine uptake.

Much evidence highlights the importance of polyamines for VSMC (vascular smooth muscle cell) proliferation and migration. Cav-1 (caveolin-1) was recently reported to regulate polyamine uptake in intestinal epithelial cells. The aim of the present study was to assess the importance of Cav-1 for VSMC polyamine uptake and its impact on cell proliferation and migration. Cav-1 KO (knockout) mouse aortic cells showed increased polyamine uptake and elevated proliferation and migration compared with WT (wild-type) cells. Both Cav-1 KO and WT cells expressed the smooth muscle differentiation markers SM22 and calponin. Cell-cycle phase distribution analysis revealed a higher proportion of Cav-1 KO than WT cells in the S phase. Cav-1 KO cells were hyper-proliferative in the presence but not in the absence of extracellular polyamines, and, moreover, supplementation with exogenous polyamines promoted proliferation in Cav-1 KO but not in WT cells. Expression of the solute carrier transporters Slc7a1 and Slc43a1 was higher in Cav-1 KO than in WT cells. ODC (ornithine decarboxylase) protein and mRNA expression as well as ODC activity were similar in Cav-1 KO and WT cells showing unaltered synthesis of polyamines in Cav-1 KO cells. Cav-1 was reduced in migrating cells in vitro and in carotid lesions in vivo. Our data show that Cav-1 negatively regulates VSMC polyamine uptake and that the proliferative advantage of Cav-1 KO cells is critically dependent on polyamine uptake. We provide proof-of-principle for targeting Cav-1-regulated polyamine uptake as a strategy to fight unwanted VSMC proliferation as observed in restenosis.

Effects of oats on plasma cholesterol and lipoproteins in C57BL/6 mice are substrain specific.

Cholesterol-lowering effects of oats have been demonstrated in both animals and human subjects. However, the crucial properties of oat-containing diets that determine their health effects need to be further investigated to optimise their use. A mouse model would be a valuable tool, but few such studies have been published to date. We investigated the effects of oat bran on plasma cholesterol and lipoproteins in two substrains of C57BL/6 mice. Western diet was made atherogenic by the addition of 0.8 % cholesterol and 0.1 % cholic acid. After 4 weeks on atherogenic diet, total plasma cholesterol had increased from 1.86-2.53 to 3.77-4.40 mmol/l. In C57BL/6NCrl mice, inclusion of 27 and 40 % oat bran reduced total plasma cholesterol by 19 and 24 %, respectively, reduced the shift from HDL to LDL+VLDL and caused increased faecal cholesterol excretion. There was no effect of oat bran on plasma levels of the inflammatory markers fibrinogen, serum amyloid A or TNF-alpha. Contrary to findings in C57BL/6NCrl mice, there was no sustained effect of oat bran (27 or 40 %) on plasma cholesterol in C57BL/6JBomTac mice after 4 weeks of feeding. Thus, C57BL/6NCrl mice fed an atherogenic diet are a good model for studies of physiological effects of oats, whereas a substrain derived from C57BL/6J, raised in a different breeding environment and likely possessing functional genetic differences from C57BL/6N, is considerably less responsive to oats. The present finding that two substrains of mice respond differently to oats is of practical value, but can also help to elucidate mechanisms of the cholesterol-lowering effect of oats.