scholarly journals High-cholesterol diet during pregnancy induces maternal vascular dysfunction in mice: potential role for oxidized LDL-induced LOX-1 and AT1 receptor activation

2020 ◽  
Vol 134 (17) ◽  
pp. 2295-2313
Author(s):  
Tamara Sáez ◽  
Floor Spaans ◽  
Raven Kirschenman ◽  
Tatsuya Sawamura ◽  
Sandra T. Davidge
Keyword(s):  
Vascular Function ◽  
Vascular Dysfunction ◽  
Oxidized Ldl ◽  
Receptor Activation ◽  
Adverse Outcomes ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Uterine Arteries ◽  
Vascular Beds

Abstract The lectin-like oxidized low-density-lipoprotein (oxLDL) receptor-1 (LOX-1) has been shown to induce angiotensin II (AngII) type 1 receptor (AT1) activation, contributing to vascular dysfunction. Preeclampsia is a pregnancy complication characterized by vascular dysfunction and increased LOX-1 and AT1 activation; however, whether LOX-1 and AT1 activity contributes to vascular dysfunction in preeclampsia is unknown. We hypothesized that increased oxLDL levels during pregnancy lead to LOX-1 activation and subsequent AT1 activation, resulting in vascular dysfunction. Pregnant wild-type (WT) and transgenic LOX-1 overexpressing (LOX-1tg) mice were fed a control diet (CD) or high-cholesterol diet (HCD, to impair vascular function) between gestational day (GD) 13.5-GD18.5. On GD18.5, AngII-induced vasoconstriction and methylcholine (MCh)-induced endothelium-dependent vasodilation responses were assessed in aortas and uterine arteries. HCD decreased fetal weight and increased circulating oxLDL/cholesterol levels in WT, but not in LOX-1tg mice. HCD did not alter AngII responsiveness or AT1 expression in both vascular beds; however, AngII responsiveness and AT1 expression were lower in aortas from LOX-1tg compared with WT mice. In aortas from WT-CD mice, acute oxLDL exposure induced AT1-mediated vasoconstriction via LOX-1. HCD impaired endothelium-dependent vasodilation and increased superoxide levels in WT aortas, but not uterine arteries. Moreover, in WT-CD mice oxLDL decreased MCh sensitivity in both vascular beds, partially via LOX-1. In summary, HCD impaired pregnancy outcomes and vascular function, and oxLDL-induced LOX-1 activation may contribute to vascular dysfunction via AT1. Our study suggests that LOX-1 could be a potential target to prevent adverse outcomes associated with vascular dysfunction in preeclampsia.

Effects of dietary flaxseed on vascular contractile function and atherosclerosis during prolonged hypercholesterolemia in rabbits

2006 ◽  
Vol 291 (6) ◽  
pp. H2987-H2996 ◽  
Author(s):  
C. M. C. Dupasquier ◽  
A.-M. Weber ◽  
B. P. Ander ◽  
P. P. Rampersad ◽  
S. Steigerwald ◽  
...  
Keyword(s):  
Vascular Function ◽  
Contractile Function ◽  
Plasma Cholesterol ◽  
Dietary Cholesterol ◽  
Relaxation Response ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Beneficial Effects ◽  
Atherosclerotic Lesions

Dietary flaxseed has significant anti-atherogenic effects. However, the limits of this action and its effects on vascular contractile function are not known. We evaluated the effects of flaxseed supplementation on atherosclerosis and vascular function under prolonged hypercholesterolemic conditions in New Zealand White rabbits assigned to one of four groups for 6, 8, or 16 wk of feeding: regular diet (RG), 10% flaxseed-supplemented diet (FX), 0.5% cholesterol-supplemented diet (CH), and 0.5% cholesterol- and 10% flaxseed-supplemented diet (CF). Cholesterol feeding resulted in elevated plasma cholesterol levels and the development of atherosclerosis. The CF group had significantly less atherosclerotic lesions in the aorta and carotid arteries after 6 and 8 wk than the CH animals. However, the anti-atherogenic effect of flaxseed supplementation was completely attenuated by 16 wk. Maximal tension induced in aortic rings either by KCl or norepinephrine was not impaired by dietary cholesterol until 16 wk. This functional impairment was not prevented by including flaxseed in the high-cholesterol diet. Aortic rings from the cholesterol-fed rabbits exhibited an impaired relaxation response to acetylcholine at all time points examined. Including flaxseed in the high-cholesterol diet completely normalized the relaxation response at 6 and 8 wk and partially restored it at 16 wk. No significant changes in the relaxation response induced by sodium nitroprusside were observed in any of the groups. In summary, dietary flaxseed is a valuable strategy to limit cholesterol-induced atherogenesis as well as abnormalities in endothelial-dependent vasorelaxation. However, these beneficial effects were attenuated during prolonged hypercholesterolemic conditions.

scholarly journals Comparison of the Protective Effects of Individual Components of Particulatedtrans-Sialidase (PTCTS), PTC and TS, against High Cholesterol Diet-Induced Atherosclerosis in Rabbits

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Shérrira M. Garavelo ◽  
Maria de Lourdes Higuchi ◽  
Jaqueline J. Pereira ◽  
Marcia M. Reis ◽  
Joyce T. Kawakami ◽  
...  
Keyword(s):  
Mycoplasma Pneumoniae ◽  
Abdominal Aorta ◽  
Oxidized Ldl ◽  
Rabbit Model ◽  
Lipid Lowering ◽  
High Cholesterol Diet ◽  
Protective Effects ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Plaque Area

Previous studies showed the presence ofMycoplasma pneumoniae(M. pneumoniae) and membrane-shed microparticles (MPs) in vulnerable atherosclerotic plaques. H&S Science and Biotechnology developed PTCTS, composed by natural particles from medicinal plants (PTC) combined withtrans-Sialidase (TS), to combat MPs andMycoplasma pneumoniae. Our aim was to determine the effects of the different components of PTCTS in a rabbit model of atherosclerosis. Rabbits were fed with high cholesterol diet for 12 weeks and treated during the last 6 weeks with either vehicle, PTC, TS, or PTCTS. Lipid profile and quantification of MPs positive forMycoplasma pneumoniaeand oxidized LDL antigens were carried out. Aortas and organs were then histologically analyzed. PTCTS reduced circulating MPs positive forMycoplasma pneumoniaeand oxidized LDL antigens, reduced the plaque area in the abdominal aorta, and caused positive remodeling of the ascendant aorta. PTC caused positive remodeling and reduced plaque area in the abdominal aorta; however, TS had a lipid lowering effect. PTCTS components combined were more effective against atherosclerosis than individual components. Our data reinforce the infectious theory of atherosclerosis and underscore the potential role of circulating MPs. Therefore, the removal ofMycoplasma-derived MPs could be a new therapeutic approach in the treatment of atherosclerosis.

Effects of high-cholesterol diet and parallel exercise training on the vascular function of rabbit aortas: a time course study

2003 ◽  
Vol 95 (3) ◽  
pp. 1194-1200 ◽  
Author(s):  
Ai-Lun Yang ◽  
Chauying J. Jen ◽  
Hsiun-ing Chen
Keyword(s):  
Nitric Oxide ◽  
Exercise Training ◽  
Vascular Function ◽  
Time Course ◽  
Early Stage ◽  
Elevated Serum ◽  
Normal Diet ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol

It is plausible to assume that exercise training, when applied early enough, can completely correct atherosclerotic defects. Using rabbit aortic specimens, we examined the effects of chronic exercise and high-cholesterol diet feeding on vascular function for different time periods. Male New Zealand White rabbits were divided into four groups: the normal diet groups with or without exercise training and the high-cholesterol diet groups with or without exercise training. Animals in high-cholesterol diet groups were fed 2% cholesterol rabbit chow for 2, 4, or 6 wk. Those in exercise training groups ran on a treadmill at 0.88 km/h for up to 40 min/day, 5 days/wk for the same period of time as the diet feeding. Thoracic aortas were isolated for functional and immunohistochemical analyses. We found that 1) although high-cholesterol diet feeding (≥2 wk) elevated serum cholesterol levels and impaired acetylcholine-evoked vasorelaxation, only the latter effect was reversed by exercise training; 2) the effects of diet and exercise on acetylcholine-evoked vasorelaxation were mainly due to altered release of nitric oxide and endothelium-derived hyperpolarizing factor; and 3) diet feeding for 4 or 6 wk caused significant lipid deposition and expression of P-selectin, VCAM-1, monocyte chemoattractant protein-1, and inducible nitric oxide synthase, which were largely reduced by exercise training. In conclusion, parallel exercise training almost completely reverses the early-stage endothelial dysfunction caused by high-cholesterol diet feeding.

Agonist-specific impairment of coronary vascular function in genetically altered, hyperlipidemic mice

1999 ◽  
Vol 276 (4) ◽  
pp. R1023-R1029 ◽  
Author(s):  
Kathryn G. Lamping ◽  
Daniel W. Nuno ◽  
David A. Chappell ◽  
Frank M. Faraci
Keyword(s):  
Nitric Oxide ◽  
Coronary Arteries ◽  
Guanylate Cyclase ◽  
Vascular Function ◽  
Soluble Guanylate Cyclase ◽  
Plasma Cholesterol ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Deficient Mice

The objectives of the present study were to 1) examine mechanisms involved in endothelium-dependent responses of coronary arteries from normal mice and 2) determine whether vascular responses of coronary arteries are altered in two genetic models of hypercholesterolemia [apolipoprotein E (apoE)-deficient mice (apoE −/−) and combined apoE and low-density lipoprotein receptor (LDLR)-deficient mice (apoE + LDLR −/−)]. Plasma cholesterol levels were higher in both apoE −/− and apoE + LDLR −/− compared with normal mice on normal and high-cholesterol diets (normal chow: normal 110 ± 5 mg/dl, apoE −/− 680 ± 40 mg/dl, apoE + LDLR −/− 810 ± 40 mg/dl; high-cholesterol chow: normal 280 ± 60 mg/dl, apoE −/− 2,490 ± 310 mg/dl, apoE + LDLR −/− 3,660 ± 290 mg/dl). Coronary arteries from normal (C57BL/6J), apoE −/−, and apoE + LDLR −/− mice were isolated and cannulated, and diameters were measured using videomicroscopy. In normal mice, vasodilation in response to ACh and serotonin was markedly reduced by 10 μM N ω-nitro-l-arginine (an inhibitor of nitric oxide synthase) or 20 μM 1 H-[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one (ODQ; an inhibitor of soluble guanylate cyclase). Vasodilation to nitroprusside, but not papaverine, was also inhibited by ODQ. Dilation of arteries from apoE −/− and apoE + LDLR −/− mice on normal diet in response to ACh was similar to that observed in normal mice. In contrast, dilation of arteries in response to serotonin from apoE −/− and apoE + LDLR −/− mice was impaired compared with normal. In arteries from both apoE −/− and apoE + LDLR −/− mice on high-cholesterol diet, dilation to ACh was decreased. In apoE + LDLR −/− mice on high-cholesterol diet, dilation of coronary arteries to nitroprusside was increased. These findings suggest that dilation of coronary arteries from normal mice in response to ACh and serotonin is dependent on production of nitric oxide and activation of soluble guanylate cyclase. Hypercholesterolemia selectively impairs dilator responses of mouse coronary arteries to serotonin. In the absence of both apoE and the LDL receptor, high levels of cholesterol result in a greater impairment in coronary endothelial function.

scholarly journals Metabolic Profiling Reveals Aggravated Non-Alcoholic Steatohepatitis in High-Fat High-Cholesterol Diet-Fed Apolipoprotein E-Deficient Mice Lacking Ron Receptor Signaling

Metabolites ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 326
Author(s):  
Joselyn N. Allen ◽  
Adwitia Dey ◽  
Jingwei Cai ◽  
Jingtao Zhang ◽  
Yuan Tian ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Apolipoprotein E ◽  
Metabolic Pathways ◽  
Receptor Activation ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
High Fat ◽  
Alcoholic Steatohepatitis ◽  
Ron Receptor

Non-alcoholic steatohepatitis (NASH) represents the progressive sub-disease of non-alcoholic fatty liver disease that causes chronic liver injury initiated and sustained by steatosis and necroinflammation. The Ron receptor is a tyrosine kinase of the Met proto-oncogene family that potentially has a beneficial role in adipose and liver-specific inflammatory responses, as well as glucose and lipid metabolism. Since its discovery two decades ago, the Ron receptor has been extensively investigated for its differential roles on inflammation and cancer. Previously, we showed that Ron expression on tissue-resident macrophages limits inflammatory macrophage activation and promotes a repair phenotype, which can retard the progression of NASH in a diet-induced mouse model. However, the metabolic consequences of Ron activation have not previously been investigated. Here, we explored the effects of Ron receptor activation on major metabolic pathways that underlie the development and progression of NASH. Mice lacking apolipoprotein E (ApoE KO) and double knockout (DKO) mice that lack ApoE and Ron were maintained on a high-fat high-cholesterol diet for 18 weeks. We observed that, in DKO mice, the loss of ligand-dependent Ron signaling aggravated key pathological features in steatohepatitis, including steatosis, inflammation, oxidation stress, and hepatocyte damage. Transcriptional programs positively regulating fatty acid (FA) synthesis and uptake were upregulated in the absence of Ron receptor signaling, whereas lipid disposal pathways were downregulated. Consistent with the deregulation of lipid metabolism pathways, the DKO animals exhibited increased accumulation of FAs in the liver and decreased level of bile acids. Altogether, ligand-dependent Ron receptor activation provides protection from the deregulation of major metabolic pathways that initiate and aggravate non-alcoholic steatohepatitis.

Hypolipidemic and antioxidant effect of Ajuga iva in rats fed a high-cholesterol diet

Planta Medica ◽  
2006 ◽  
Vol 72 (11) ◽  
Author(s):  
MA Lacaille-Dubois ◽  
A Chenni ◽  
DA Yahia ◽  
FO Boukortt ◽  
J Prost ◽  
...  
Keyword(s):  
Antioxidant Effect ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol
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