scholarly journals Sex Differences in Presynaptic Density and Neurogenesis in Middle-Aged ApoE4 and ApoE Knockout Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
A. Rijpma ◽  
D. Jansen ◽  
I. A. C. Arnoldussen ◽  
X. T. Fang ◽  
M. Wiesmann ◽  
...  
Keyword(s):  
Sex Differences ◽  
Molecular Layer ◽  
Compensatory Mechanism ◽  
Wild Type ◽  
Middle Aged ◽  
Apoe Knockout Mice ◽  
Presynaptic Density ◽  
Apoe Ko Mice ◽  
Apoe Genotypes ◽  
Apoe Ko

Atherosclerosis and apolipoprotein E ε4 (APOE4) genotype are risk factors for Alzheimer’s disease (AD) and cardiovascular disease (CVD). Sex differences exist in prevalence and manifestation of both diseases. We investigated sex differences respective to aging, focusing on cognitive parameters in apoE4 and apoE knockout (ko) mouse models of AD and CVD. Presynaptic density and neurogenesis were investigated immunohistochemically in male and female apoE4, apoE ko, and wild-type mice. Middle-aged female apoE4 mice showed decreased presynaptic density in the inner molecular layer of the dentate gyrus of the hippocampus. Middle-aged female apoE ko mice showed a trend towards increased neurogenesis in the hippocampus compared with wild-type mice. No differences in these parameters could be observed in middle-aged male mice. Specific harmful interactions between apoE4 and estrogen could be responsible for decreased presynaptic density in female apoE4 mice. The trend of increased neurogenesis found in female apoE ko mice supports previous studies suggesting that temporarily increased amount of synaptic contacts and/or neurogenesis is a compensatory mechanism for synaptic failure. To our knowledge, no other studies investigating presynaptic density in aging female apoE4 or apoE ko mice are available. Sex-specific differences between APOE genotypes could account for some sex differences in AD and CVD.

Abstract 911: Lacking SOCS3 Gene in Macrophages Prevents the Development of Atherosclerosis in ApoE Deficient Mice

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Tomoka Yamamoto ◽  
Hideo Yasukawa ◽  
Mitsuhisa Koga ◽  
Yusuke Sugi ◽  
Daisuke Fukui ◽  
...  
Keyword(s):  
Western Blot ◽  
Immunohistochemical Staining ◽  
Oxidized Ldl ◽  
Enzyme Linked Immunosorbent Assay ◽  
Wild Type ◽  
Stat3 Signaling ◽  
Ldl Uptake ◽  
Apoe Ko Mice ◽  
Deficient Mice ◽  
Apoe Ko

Background : Atherosclerosis is now generally accepted as a chronic inflammatory disease characterized by accumulation of blood-derived macrophages in the arterial wall. It has been shown that suppressor of cytokine signaling 3 (SOCS3) is an intrinsic negative regulator of interleukin-6 (IL-6)-STAT3 signaling that plays an essential role in inflammatory response. In the present study, we determined whether STAT3-mediated IL-6 signaling and SOCS3 within the macrophages would play an important role in the development of atherosclerosis. Methods and Results : We examined the activation of STAT3 and expressions of IL-6 family cytokines and SOCS3 in the aorta of apolipoprotein E knockout mice (ApoE-KO) and control mice by western blot, immunohistochemical staining and RT-PCR. Western blot revealed that STAT3 is phosphorylated in the atherosclerotic lesions from ApoE-KO mice but not in those from control mice. Dual immunohistochemical staining revealed that phosphorylated STAT3 and macrophage marker, MOMA2, were co-expressed in the atherosclerotic plaque in ApoE-KO deficient mice, suggesting that the STAT3 signaling pathway within the macrophages was activated in atherosclerosis. Next, to investigate the role of STAT3-mediated IL-6 signaling and SOCS3 in macrophages during atherogenesis, we created ApoE-KO mice with a macrophage-restricted deletion of SOCS3 gene (ApoE/SOCS3-KO). We found that atherosclerotic lesion area by oil-red O staining was significantly reduced in ApoE/SOCS3-KO (n=17) compared with control ApoE-KO mice (n=13) (4.63±0.43 vs. 8.29±0.50 %, p<0.01). In in vitro analyses, enzyme-linked immunosorbent assay revealed that LPS-induced TNF-alpha production were significantly smaller in SOCS3 deficient macrophages compared with wild type macrophages (n=8, 2238±155 vs. 992±83 pg/ml, p<0.01). Also we found that IL-6-induced oxidized-LDL uptake was 42% reduced in SOCS3 deficient macrophages compared with wild type macrophages (p<0.01). Conclusion: Our data show that the deletion of SOCS3 in macrophages prevents the development of atherosclerosis in mice, possibly by inhibiting the inflammatory cytokine production and oxidized-LDL uptake in macrophages.

Abstract 5492: Tetrahydrobiopterin (BH4) Improves Endothelial Cell Survival After Vascular Injury

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Ruth Rinze ◽  
Ziad A Ali ◽  
Gillian Douglas ◽  
Nicholas J Alp ◽  
Keith M Channon
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Survival ◽  
Vascular Injury ◽  
Neointimal Hyperplasia ◽  
Wild Type ◽  
Endothelial Cell Survival ◽  
Apoe Ko Mice ◽  
Apoe Ko

Endothelial cell loss, survival and regeneration are important aspects of the response to vascular injury leading to neointimal hyperplasia and accelerated atherosclerosis. Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS), is a key regulator of endothelial cell biology and has been shown to prevent endothelial cell apoptosis. The cofactor tetrahydrobiopterin (BH4) is essential for eNOS catalytic activity but its impact on endothelial cell survival and regeneration remains unclear. We investigated the effect of BH4 on endothelial cell survival and vascular remodelling using ApoE-KO mice with transgenic endothelial-targeted overexpression of GTP cyclohydrolase 1 (GCH), the rate limiting enzyme of BH4 synthesis, and with endothelial specific transgenic expression of the LacZ reporter gene. Using venous bypass grafts as an in vivo model of acute vascular injury, we observed that endothelial-specific augmentation of BH4 in GCH/ApoE-KO mice improved survival of vein graft-derived endothelial cells and reduced neointimal hyperplasia. To address the hypothesis that augmentation of BH4 increases the capacity of endothelial cells from GCH/ApoE-KO mice to survive vascular injury, we cultured primary lung endothelial cells from mice expressing the GCH transgene and wild type littermates. Endothelial cells, isolated by immunomagnetic beads, were positive for CD31, CD102 and Tie2. Protein levels of eNOS were not different between wild type and GCH mice. BH4 levels were selectively increased in pulmonary endothelial cells from GCH mice, > 10-fold, compared with a 3-fold increase in total lung tissue BH4. There was no difference in total lung endothelial cell content or amount of isolated cells between ApoE-KO and GCH/ApoE-KO mice, determined by Tie2-driven β-galactosidase activity. However, after 3 days of culture both total endothelial cell number and number of endothelial cell colonies in GCH/ApoE-KO were significantly increased (236% ± 47 p=0.028 and 195% ± 28 p=0.014 respectively, n=5) whereas mean colony size remained unchanged. These observations indicate an important role for BH4 in endothelial cell survival and endothelial regeneration, and identify BH4 as a potential therapeutic target in vascular injury states.

scholarly journals Sex Differences in Association Between Anti-Hypertensive Medications and Risk of COVID-19 in Middle-Aged and Older Adults

Drugs & Aging ◽  
2021 ◽  
Author(s):  
Yue Ma ◽  
Yuan Zhang ◽  
Shu Li ◽  
Hongxi Yang ◽  
Huiping Li ◽  
...  
Keyword(s):  
Older Adults ◽  
Sex Differences ◽  
Middle Aged

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

Lipids ◽  
2015 ◽  
Vol 50 (9) ◽  
pp. 839-846 ◽  
Author(s):  
Futian Tang ◽  
Xiaoqiang Li ◽  
Yali Gui ◽  
Cuiling Qi ◽  
Meili Lu ◽  
...  
Keyword(s):  
Apoe Ko Mice ◽  
Apoe Ko

scholarly journals Sex Differences in Perceived Stress and Early Recovery in Young and Middle-Aged Patients With Acute Myocardial Infarction

Circulation ◽  
2015 ◽  
Vol 131 (7) ◽  
pp. 614-623 ◽  
Author(s):  
Xiao Xu ◽  
Haikun Bao ◽  
Kelly Strait ◽  
John A. Spertus ◽  
Judith H. Lichtman ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Sex Differences ◽  
Perceived Stress ◽  
Middle Aged ◽  
Early Recovery ◽  
Aged Patients

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

2008 ◽  
Vol 294 (1) ◽  
pp. F120-F129 ◽  
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.

scholarly journals 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

2012 ◽  
Vol 109 (1) ◽  
pp. 17-24 ◽  
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.

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

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
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.

scholarly journals Sex-differences in age-related grip strength decline: A 10-year longitudinal study of community-living middle-aged and older Japanese

2016 ◽  
Vol 5 (1) ◽  
pp. 87-94 ◽  
Author(s):  
Rumi Kozakai ◽  
Fujiko Ando ◽  
Heung Youl Kim ◽  
Atsumu Yuki ◽  
Rei Otsuka ◽  
...  
Keyword(s):  
Sex Differences ◽  
Longitudinal Study ◽  
Grip Strength ◽  
Community Living ◽  
Middle Aged ◽  
Age Related

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

2002 ◽  
Vol 11 (1) ◽  
pp. 21-30 ◽  
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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