Fenretinide treatment in APOE-KO mice severely alters erythrocyte turnover and causes a dramatic increase of circulating leukocytes resulting in a worsened atherosclerosis development

Leishmania major infection of resistant mice causes a self-limited lesion characterized by macrophage activation and a Th1 proinflammatory response. Atherosclerosis is an inflammatory disease involving hypercholesterolemia and macrophage activation. In this study, we evaluated the influence of L. major infection on the development of atherosclerosis using atherosclerosis-susceptible apolipoprotein E-deficient (apoE KO) mice. After 6 weeks of infection, apoE KO mice exhibited reduced footpad swelling and parasitemia similar to C57BL/6 controls, confirming that both strains are resistant to infection with L. major. L. major-infected mice had increased plasma cholesterol levels and reduced triacylglycerols. With regard to atherosclerosis, noninfected mice developed only fatty streak lesions, while the infected mice presented with advanced lesions containing a necrotic core and an abundant inflammatory infiltrate. CD36 expression was increased in the aortic valve of the infected mice, indicating increased macrophage activation. In conclusion, L. major infection, although localized and self-limited in resistant apoE KO mice, has a detrimental effect on the blood lipid profile, increases the inflammatory cell migration to atherosclerotic lesions, and promotes atherogenesis. These effects are consequences of the stimulation of the immune system by L. major, which promotes the inflammatory components of atherosclerosis, which are primarily the parasite-activated macrophages.

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Rupatadine Does Not Affect Atherosclerosis Development In Apoe-Ko Mice

Atherosclerosis ◽

10.1016/j.atherosclerosis.2019.06.771 ◽

2019 ◽

Vol 287 ◽

pp. e250-e251

Author(s):

G. Chiesa ◽

M. Busnelli ◽

L. Capparini ◽

S. Manzini

Keyword(s):

Atherosclerosis Development ◽

Apoe Ko Mice ◽

Apoe Ko

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p110Delta Inhibits Monocyte Infiltration by Thioglycollate-Induced Periotoneal Inflammation but Not HCD-Induced Inflammation and Atherosclerosis in APOE KO Mice

Lipids ◽

10.1007/s11745-015-4026-8 ◽

2015 ◽

Vol 50 (9) ◽

pp. 839-846 ◽

Cited By ~ 2

Author(s):

Futian Tang ◽

Xiaoqiang Li ◽

Yali Gui ◽

Cuiling Qi ◽

Meili Lu ◽

...

Keyword(s):

Apoe Ko Mice ◽

Apoe Ko

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Altered TP receptor function in isolated, perfused kidneys of nondiabetic and diabetic ApoE-deficient mice

AJP Renal Physiology ◽

10.1152/ajprenal.00111.2007 ◽

2008 ◽

Vol 294 (1) ◽

pp. F120-F129 ◽

Cited By ~ 22

Author(s):

Frédéric Michel ◽

Serge Simonet ◽

Christine Vayssettes-Courchay ◽

Florence Bertin ◽

Patricia Sansilvestri-Morel ◽

...

Keyword(s):

Angiotensin Ii ◽

Kidney Disease ◽

Renal Diseases ◽

Receptor Ligands ◽

Tp Receptor ◽

Vasodilator Activity ◽

Tp Receptors ◽

Apoe Ko Mice ◽

Apoe Ko ◽

Biphasic Responses

Early manifestations of kidney disease occur in atherosclerosis and activation of TP (thromboxane A2) receptors is implicated in atherosclerotic, diabetes, and renal diseases. The purpose of the present study was to analyze, in isolated, perfused mouse kidneys, the participation of TP receptors in renal vasoconstrictions and vasodilatations. In kidneys, taken from wild-type C57BL6, apolipoprotein E-deficient (ApoE-KO) and diabetic ApoE-KO mice, changes in perfusion pressure were recorded. Constrictions to TP receptor ligands U 46619, arachidonic acid, PGH2, and 8-iso-PGF2α, but not those to angiotensin II, endothelin, or norepinephrine, were inhibited by the selective TP receptor antagonist Triplion (S 18886; 10 nM). Acetylcholine and prostacyclin evoked biphasic responses during methoxamine constrictions; the constrictor part was blocked by Triplion. In ApoE-KO mouse kidneys, compared with C57BL6, a specific decrease in norepinephrine response and no modification in dilator responses were observed. In diabetic ApoE-KO mouse kidneys, constrictions to U 46619 and those to 8-iso-PGF2α were significantly and selectively augmented, without modification in the expression of the TP receptor, and again without any significant change in vasodilator activity. Thus TP receptors are functional, and their activation is not involved in norepinephrine, endothelin, and angiotensin II vasoconstrictions but is implicated in the unusual vasoconstrictions to acetylcholine and prostacyclin. Increased responsiveness of TP receptors occurs in diabetic ApoE-KO mouse kidneys. Thus early changes in TP receptor-mediated vasoconstrictor activity may participate in the development of kidney disease in atherosclerosis and diabetes.

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Beneficial effects of the active principle component of Korean cabbage kimchi via increasing nitric oxide production and suppressing inflammation in the aorta of apoE knockout mice

British Journal Of Nutrition ◽

10.1017/s0007114512000633 ◽

2012 ◽

Vol 109 (1) ◽

pp. 17-24 ◽

Cited By ~ 13

Author(s):

Jeong Sook Noh ◽

Yung Hyun Choi ◽

Yeong Ok Song

Keyword(s):

Treated Group ◽

Atherogenic Diet ◽

Control Group ◽

Active Principle ◽

Enos Expression ◽

Beneficial Effects ◽

Enos Uncoupling ◽

No Bioavailability ◽

Apoe Ko Mice ◽

Apoe Ko

The present study investigated the effects of 3′-(4′-hydroxyl-3′,5′-dimethoxyphenyl)propionic acid (HDMPPA), the active principle compound of kimchi, on vascular damage in the experimental atherosclerotic animal. HDMPPA was administrated by an intraperitoneal injection of 10 mg/kg per d for 8 weeks to apoE knockout (KO) mice with an atherogenic diet containing 1 % cholesterol, and its effects were compared with vehicle-treated control mice. HDMPPA increased NO content in the aorta, accompanied by a decrease in reactive oxygen species (ROS) concentration. Furthermore, in the HDMPPA-treated group, aortic endothelial NO synthase (eNOS) expression was up-regulated compared with the control group. These results suggested that HDMPPA could maintain NO bioavailability through an increasing eNOS expression and preventing NO degradation by ROS. Furthermore, HDMPPA treatment in apoE KO mice inhibited eNOS uncoupling through an increase in vascular tetrahydrobiopterin content and a decrease in serum asymmetric dimethylarginine levels. Moreover, HDMPPA ameliorates inflammatory-related protein expression in the aorta of apoE KO mice. Therefore, the present study suggests that HDMPPA, the active compound of kimchi, a Korean functional food, may exert its vascular protective effect through the preservation of NO bioavailability and suppression of the inflammatory response.

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Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition

BioMed Research International ◽

10.1155/2016/5438589 ◽

2016 ◽

Vol 2016 ◽

pp. 1-14 ◽

Cited By ~ 3

Author(s):

Zhu Zhu ◽

Bingxuan Hua ◽

Zhanxian Shang ◽

Gongsheng Yuan ◽

Lirong Xu ◽

...

Keyword(s):

Lipid Metabolism ◽

Serum Lipids ◽

Clock Genes ◽

Plaque Formation ◽

Sirtuin 1 ◽

Atheromatous Plaque ◽

Circadian Oscillation ◽

Lighting Condition ◽

Apoe Ko Mice ◽

Apoe Ko

Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice.Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice) by altering exposure to light. C57 BL/6J mice (C57 mice) and ApoE-KO mice (ApoE-KO mice) exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1) levels and rhythmicity.Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice.Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation.

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Angiotensin II is associated with activation of NF-κB-mediated genes and downregulation of PPARs

Physiological Genomics ◽

10.1152/physiolgenomics.00062.2002 ◽

2002 ◽

Vol 11 (1) ◽

pp. 21-30 ◽

Cited By ~ 197

Author(s):

Doris M. Tham ◽

Baby Martin-McNulty ◽

Yi-xin Wang ◽

Dennis W. Wilson ◽

Ronald Vergona ◽

...

Keyword(s):

Angiotensin Ii ◽

Adhesion Molecule ◽

Vascular Inflammation ◽

Aortic Aneurysms ◽

Intercellular Adhesion Molecule ◽

Ang Ii ◽

Inflammatory Genes ◽

Apoe Ko Mice ◽

Apoe Ko

Angiotensin II (ANG II) promotes vascular inflammation through nuclear factor-κB (NF-κB)-mediated induction of pro-inflammatory genes. The role of peroxisome proliferator-activated receptors (PPARs) in modulating vascular inflammation and atherosclerosis in vivo is unclear. The aim of the present study was to examine the effects of ANG II on PPARs and NF-κB-dependent pro-inflammatory genes in the vascular wall in an in vivo model of atherosclerosis and aneurysm formation. Six-month-old male apolipoprotein E-deficient (apoE-KO) mice were treated with ANG II (1.44 mg/kg per day for 30 days). ANG II enhanced vascular inflammation, accelerated atherosclerosis, and induced formation of abdominal aortic aneurysms. These effects of ANG II in the aorta were associated with downregulation of both PPAR-α and PPAR-γ mRNA and protein and an increase in transcription of monocyte chemotactic protein-1 (MCP-1), macrophage-colony stimulating factor (M-CSF), endothelial-selectin (E-selectin), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) throughout the entire aorta. ANG II also activated NF-κB with increases in both p52 and p65 NF-κB subunits. In summary, these in vivo results indicate that ANG II, through activation of NF-κB-mediated pro-inflammatory genes, promotes vascular inflammation, leading to acceleration of atherosclerosis and induction of aneurysm in apoE-KO mice. Downregulation of PPAR-α and -γ by ANG II may diminish the anti-inflammatory potential of PPARs, thus contributing to enhanced vascular inflammation.

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The reciprocal relationship between adiponectin and LOX-1 in the regulation of endothelial dysfunction in ApoE knockout mice

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01096.2009 ◽

2010 ◽

Vol 299 (3) ◽

pp. H605-H612 ◽

Cited By ~ 28

Author(s):

Xiuping Chen ◽

Hanrui Zhang ◽

Steve McAfee ◽

Cuihua Zhang

Keyword(s):

Endothelial Cells ◽

Endothelial Dysfunction ◽

Sodium Nitroprusside ◽

Oxidized Ldl ◽

Reciprocal Relationship ◽

Reciprocal Regulation ◽

Tnf Α ◽

Ldl Uptake ◽

Apoe Ko Mice ◽

Apoe Ko

We hypothesized that the reciprocal association between adiponectin and lectin-like oxidized LDL (ox-LDL) receptor (LOX)-1 contributes to the regulation of aortic endothelial dysfunction in atherosclerosis. To test this hypothesis, endothelium-dependent (ACh) and endothelium-independent (sodium nitroprusside) vasorelaxation of isolated aortic rings from control mice, apolipoprotein E (ApoE) knockout (KO) mice, and ApoE KO mice treated with either adiponectin (15 μg·day−1·mouse−1 sc for 8 days) or neutralizing antibody to LOX-1 (anti-LOX-1, 16 μg/ml, 0.1 ml/mouse ip for 7 days) were examined. Although vasorelaxation to sodium nitroprusside was not different between control and ApoE KO mice, relaxation to ACh was impaired in ApoE KO mice. Adiponectin and anti-LOX-1 restored nitric oxide-mediated endothelium-dependent vasorelaxation in ApoE KO mice. Aortic ROS formation and ox-LDL uptake were increased in ApoE KO mice. Both adiponectin and anti-LOX-1 treatment reduced ROS production and aortic ox-LDL uptake. In mouse coronary artery endothelial cells, TNF-α incubation increased endothelial LOX-1 expression. Adiponectin reduced TNF-α-induced LOX-1 expression. Consistently, in ApoE KO mice, adiponectin treatment reversed elevated LOX-1 expression in aortas. Immunofluorescence staining showed that adiponectin was mainly colocalized with endothelial cells. Although adiponectin expression was lower in ApoE KO versus control mice, anti-LOX-1 increased aortic adiponectin expression, suggesting a reciprocal regulation between adiponectin and LOX-1. Moreover, both adiponectin and anti-LOX-1 reduced NF-κB expression in ApoE KO mice. Thus, adiponectin and LOX-1 may converge on NF-κB signaling to regulate their function. In conclusion, our results indicate that the reciprocal regulation between adiponectin and LOX-1 amplifies oxidative stress and ox-LDL uptake, leading to endothelial dysfunction in atherosclerosis.

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