scholarly journals Lipoprotein glomerulopathy induced by ApoE Kyoto mutation in ApoE-deficient mice

2020 ◽  
Author(s):  
Hongyan Wu ◽  
Jing Yang ◽  
Yun-Qiang Liu ◽  
Song Lei ◽  
Mei Yang ◽  
...  
Keyword(s):  
Murine Model ◽  
Recombinant Adenovirus ◽  
Serum Triglyceride ◽  
Multiple Time ◽  
Creatinine Ratio ◽  
Pathogenic Role ◽  
Lipoprotein Glomerulopathy ◽  
Albumin Creatinine Ratio ◽  
Apoe Kyoto ◽  
Deficient Mice

Abstract Background: Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant kidney disease that is most commonly caused by mutations in ApoE Kyoto (p.R43C) and ApoE Sendai (p.R163P). Differences in phenotype among the various ApoE mutations have been suggested, but the pathogenic role of ApoE Kyoto has not been validated in an animal model. This study intended to establish an ApoE Kyoto murine model and to further compare the pathologic differences between ApoE Kyoto and ApoE Sendai.Methods: Male ApoE-deficient mice, 3 months of age, were divided into five groups, including the Ad-ApoE Sendai, Ad-ApoE Kyoto, Ad-ApoE3, Ad-eGFP, and ApoE (−/−) groups. The first four groups received recombinant adenovirus that contained the entire coding regions of the human ApoE Sendai and ApoE Kyoto, apoE3, and eGFP genes, respectively. Fasting blood and urine samples were collected at multiple time points. Lipid profiles and urine albumin–creatinine ratio were measured. Renal and aortic histopathologic alterations were analyzed.Results: After virus injection, plasma human ApoE was detected and rapidly reached the maximum level at 4–6 days in the Ad-ApoE Kyoto and Ad-ApoE Sendai groups (17.4 ± 3.1 µg/mL vs.: 22.2 ± 4.5 µg/mL, respectively) and at 2 days in the Ad-apoE3 group (38.4 µg/mL). The serum total cholesterol decreased by 63%, 65%, and 73% in the Ad-ApoE Kyoto, Ad-ApoE Sendai, and Ad-apoE3 groups, respectively. There were no significant changes in serum triglyceride and urinary albumin–creatinine ratio among the five groups. Typical lipoprotein thrombi with positive ApoE staining were detected in the ApoE Kyoto and ApoE Sendai groups. The Oil-red O-positive glomerular area tended to be higher in the Ad-ApoE Kyoto group (9.2%) than in the Ad-ApoE Sendai (3.9%), Ad-apoE3 (4.8%), Ad-eGFP (2.9%), and ApoE (−/−) (3.6%) groups. The atherosclerotic plaque area in the aorta was lower in the group injected with various ApoE mutations than in the group without injection of ApoE mutation.Conclusions: In this animal study, we first established an ApoE Kyoto mutation murine model and confirmed its pathogenic role in LPG. Our results suggested that LPG may be more severe with the ApoE Kyoto than with the ApoE Sendai.

scholarly journals Lipoprotein glomerulopathy induced by ApoE Kyoto mutation in ApoE-deficient mice

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hongyan Wu ◽  
Jing Yang ◽  
Yun-Qiang Liu ◽  
Song Lei ◽  
Mei Yang ◽  
...  
Keyword(s):  
Murine Model ◽  
Recombinant Adenovirus ◽  
Serum Triglyceride ◽  
Multiple Time ◽  
Creatinine Ratio ◽  
Pathogenic Role ◽  
Lipoprotein Glomerulopathy ◽  
Albumin Creatinine Ratio ◽  
Apoe Kyoto ◽  
Deficient Mice

AbstractBackgroundLipoprotein glomerulopathy (LPG) is a rare autosomal dominant kidney disease that is most commonly caused by mutations in ApoE Kyoto (p.R43C) and ApoE Sendai (p.R163P). Differences in phenotype among the various ApoE mutations have been suggested, but the pathogenic role of ApoE Kyoto has not been validated in an animal model. This study intended to establish an ApoE Kyoto murine model and to further compare the pathologic differences between ApoE Kyoto and ApoE Sendai.MethodMale ApoE-deficient mice, 3 months of age, were divided into five groups, including the AD-ApoE Sendai, AD-ApoE Kyoto, AD-ApoE3, AD-eGFP, and ApoE (−/−) groups. The first four groups received recombinant adenovirus that contained the entire coding regions of the humanApoE SendaiandApoE Kyoto,apoE3, andeGFPgenes, respectively. Fasting blood and urine samples were collected at multiple time points. Lipid profiles and urine albumin–creatinine ratio were measured. Renal and aortic histopathologic alterations were analyzed.ResultsAfter virus injection, plasma human ApoE was detected and rapidly reached the maximum level at 4–6 days in the AD-ApoE Kyoto and AD-ApoE Sendai groups (17.4 ± 3.1 µg/mL vs.: 22.2 ± 4.5 µg/mL, respectively) and at 2 days in the AD-ApoE3 group (38.4 µg/mL). The serum total cholesterol decreased by 63%, 65%, and 73% in the AD-ApoE Kyoto, AD-ApoE Sendai and AD-ApoE3 groups, respectively. There were no significant changes in serum triglyceride and urinary albumin–creatinine ratio among the five groups. Typical lipoprotein thrombi with positive ApoE staining were detected in the AD-ApoE Kyoto and AD-ApoE Sendai groups. The Oil-red O-positive glomerular area tended to be higher in the AD-ApoE Kyoto group (9.2%) than in the AD-ApoE Sendai (3.9%), AD-ApoE3 (4.8%), AD-eGFP (2.9%), and ApoE (−/−) (3.6%) groups. The atherosclerotic plaque area in the aorta was lower in the group injected with various ApoE mutations than in the group without injection of ApoE mutation.ConclusionsIn this animal study, we first established an ApoE Kyoto mutation murine model and confirmed its pathogenic role in LPG. Our results suggested that LPG may be more severe with the ApoE Kyoto than with the ApoE Sendai.

Abstract 14859: IL17 Contribute to the Atherosclerotic Development and the Initiation of Chronic Kidney Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Yusuke Tanigaito ◽  
Kayoko Sato ◽  
Kazutaka Kitamura ◽  
Atsuko Futase ◽  
Keiko Fukushima ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
T Cells ◽  
Kidney Disease ◽  
High Fat Diet ◽  
Inflammatory Cytokine ◽  
Urinary Albumin ◽  
Creatinine Ratio ◽  
High Fat ◽  
Albumin Creatinine Ratio ◽  
Deficient Mice

Introduction: Recent studies suggested that the atherogenic state correlated with progression of chronic kidney disease (CKD). However, it is not known whether sustained status of chronic inflammation in atherosclerosis is closely linked to the development of CKD. Hypothesis: Inflammatory cytokine producing-T cells in the advanced atherosclerosis induced the dysfunction of podocytes. Methods/Results: Eighteen-week-old apolipoprotein E-deficient mice (Control) were fed with high-fat diet for 8W (ApoE) and compared to IL17/ApoE-double deficient mice fed with high-fat diet (DKO). Sudan staining of aorta revealed the atherosclerotic lesion was increased in ApoE compared to Control, and inhibited in DKO. Activated IFNγ + CD4 T cells (Th1) and IL17 + CD4 T cells (Th17) were significantly increased in ApoE compared to DKO by FACS. Immunohistochemistry of aortic sinus showed many Th1 and Th17 were infiltrated in the atherosclerotic plaque in ApoE, however, inflammatory infiltrates were inhibited in DKO. Furthermore, the urinary albumin/creatinine ratio was increased significantly in ApoE compared to DKO. Th1 and Th17 were correlated with the urinary albumin/creatinine ratio, and many Th1 and Th17 were observed in the glomeruli. Next, to investigate whether the inflammatory cytokine induced dysfunction of podocytes were involved in proteinuria, we investigated nephrin, podocin, and phosphorylated nephrin in the kidney by Western blots and immunohistochemistry. The decreased phosphorylated neprin in ApoE were recovered in DKO. Finally, we confirmed that the morphological changed of podocytes in ApoE were improved in DKO by electron microscopy. Conclusion: Recruitments of IFNγ + Th1 and IL17 + Th17 T cells might aggravate atherosclerosis acceleration and induce the initiation of glomerular tissue damage.

Defective lung CD8+ T cells lacking NFATc2 induced lung metastasis in NFATc2 deficient mice in a bronchoalveolar adenocarcinoma murine model

Pneumologie ◽  
2007 ◽  
Vol 61 (01) ◽  
Author(s):  
JH Maxeiner ◽  
R Karwot ◽  
K Sauer ◽  
P Scholtes ◽  
R Wiewrodt ◽  
...  
Keyword(s):  
T Cells ◽  
Lung Metastasis ◽  
Cd8 T Cells ◽  
Murine Model ◽  
Deficient Mice

scholarly journals Is there a relationship between sleep apnoea and microalbuminuria?

2021 ◽  
Author(s):  
Melek Cihanbeylerden ◽  
Melike Bağnu Yüceege
Keyword(s):  
Microvascular Complications ◽  
Sleep Apnoea ◽  
Urinary Albumin ◽  
Control Group ◽  
Creatinine Ratio ◽  
Microvascular Damage ◽  
Metabolic Complications ◽  
Albumin Creatinine Ratio ◽  
Obstructive Sleep ◽  
Significant Difference

Abstract Introduction Obstructive sleep apnoea (OSA) is a cause of hypoxia, and the correlation between hypoxia and microvascular complications is well known. Microalbuminuria (MAU) is a marker for endovascular dysfunction and an indicator of cardiovascular events and all-cause mortality in the general population. The aim of this study was to investigate the relationship between microvascular damage and the metabolic complications of OSA based on the presence of MAU. Material and method Urinary albumin/creatinine ratio (ACR) and microalbumin level were examined in patients with an apnoea-hypopnoea index (AHI) greater than 5/h (study group) and in patients with an AHI less than 5/h (control group). The exclusion criteria were other possible causes of MAU (hypertension, nephropathy, coronary artery disease, and severe thyroid dysfunction). Results Of 103 patients enrolled, 80 formed the group with OSA and 23 served as controls. According to the AHI values, the patients were divided into four groups as normal, mild, moderate and severe. There was no significant difference between the four groups in terms of the microalbumin level and urinary albumin/creatinine ratio. Conclusion In this study, no significant relationship was found between MAU and sleep apnoea.

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