scholarly journals CRISPR/Cas9-mediated knockout of APOC3 stabilizes plasma lipids and inhibits atherosclerosis in rabbits

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Yiwen Zha ◽  
Yaoyao Lu ◽  
Ting Zhang ◽  
Kunning Yan ◽  
Wenwen Zhuang ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Plasma Lipids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Control Group ◽  
Atherosclerotic Plaques ◽  
Exon 2 ◽  
Apolipoprotein C3 ◽  
Cholesterol Levels ◽  
Normal Chow

Abstract Background High levels of apolipoprotein C3 (APOC3) can lead to hypertriglyceridemia, which increases the risk of cardiovascular disease. We aim to create APOC3-knockout (KO) rabbits and explore the effects of APOC3 deletion on the occurrence and development of atherosclerosis. Methods An sgRNA anchored to exon 2 of APOC3 was designed to edit embryo genomes using the CRISPR/Cas9 system. The founder rabbits were sequenced, and their lipid profile, inflammatory cytokines, and atherosclerotic plaques were analyzed. Results When given a normal chow (NC) diet, all APOC3-KO rabbits had 50% lower triglyceride (TG) levels than those of the matched age control group. Additionally, their plasma lipoprotein lipase increased. When fed a high-fat diet, APOC3 deficiency was observed to be more conducive to the maintenance of plasma TG, total cholesterol, and low-density lipoprotein cholesterol levels, and the inhibition of the inflammatory response and the protection against atherosclerosis in rabbits. Conclusion APOC3 deficiency can delay the formation of atherosclerosis-induced HFD in rabbits, indicating this is a novel therapeutic target to treat atherosclerosis.

scholarly journals CRISPR/Cas9-Mediated Knockout of APOC3 Stabilizes Plasma Lipids and Inhibits Atherosclerosis in Rabbits

2021 ◽  
Author(s):  
Yiwen Zha ◽  
Yaoyao Lu ◽  
Ting Zhang ◽  
Kunning Yan ◽  
Wenwen Zhuang ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Plasma Lipids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Control Group ◽  
Atherosclerotic Plaques ◽  
Low Density Lipoprotein Cholesterol ◽  
Exon 2 ◽  
Apolipoprotein C3 ◽  
Normal Chow

Abstract Background: High levels of apolipoprotein C3 (APOC3) can lead to hypertriglyceridemia, which increases the risk of cardiovascular disease. We aim to create APOC3 knockout (KO) rabbits and explore the effects of APOC3 deletion on the occurrence and development of atherosclerosis.Methods: A sgRNA anchored to exon 2 of APOC3 was designed to edit embryos using the CRISPR/Cas9 system. The founder rabbits were sequenced, and their lipid profile, inflammatory cytokines and atherosclerotic plaques were analyzed.Results: When given a normal chow (NC) diet, all APOC3 KO rabbits had low plasma TG level, which was two times lower than that of the matched age control group. Additionally, their plasma lipoprotein lipase (LPL) increased. When fed a high-fat diet (HFD), it was observed that APOC3 deficiency was more conducive to the maintenance of plasma TG, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in rabbits, the inhibition of inflammatory response and the protection of atherosclerosis in rabbits.Conclusion: APOC3 KO rabbit models can be obtained with the CRISPR/Cas9 system to combat the formation of HFD-induced atherosclerosis, indicating a novel therapeutic target to treat atherosclerosis.

Atorvastatin normalizes endothelial function in healthy smokers

2006 ◽  
Vol 111 (1) ◽  
pp. 87-91 ◽  
Author(s):  
Stefan Agewall ◽  
Åsa Hernberg
Keyword(s):  
Endothelial Function ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
Control Group ◽  
Flow Mediated Dilation ◽  
Atorvastatin Treatment ◽  
Cholesterol Levels ◽  
Smoking Group ◽  
To Receive

Endothelial function is known to predict cardiovascular disease. The aim of the present study was to examine whether endothelial function in smokers with normal cholesterol levels could be normalized by treatment with 80 mg of atorvastatin in comparison with a control group. Healthy smokers (n=20) and non-smokers (n=20) were randomized to receive 80 mg of atorvastatin or placebo in an open randomized cross-over study, followed by measurement of endothelial functional [FMD (flow-mediated dilation)]. At baseline, smokers had a lower FMD compared with the non-smoking group (2.2±0.5 and 4.5±0.8% respectively; P<0.05). In the smoking group, FMD increased significantly (P<0.05) to 4.0±0.8% during treatment with atorvastatin and returned to basal levels during placebo (2.3±0.6%). In the non-smoking group, FMD was unaffected by both atorvastatin and placebo. The net change of total cholesterol or LDL (low-density lipoprotein)-cholesterol was not associated with the net change in FMD when the study group was considered as a whole or the smoking group was considered separately. In conclusion, improved endothelial function was observed in a group of smokers when they were received 80 mg of atorvastatin, whereas atorvastatin had no effect on endothelial function in the non-smoking group. The improved FMD among smokers was independent of the decrease in LDL-cholesterol during atorvastatin treatment. The results show that poor endothelial function in smokers with normal lipid levels can be improved by a statin treatment.

scholarly journals Intermittent Fasting Inhibits High-Fat Diet–Induced Atherosclerosis by Ameliorating Hypercholesterolemia and Reducing Monocyte Chemoattraction

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuanli Chen ◽  
Jiamin Su ◽  
Yali Yan ◽  
Qian Zhao ◽  
Jialing Ma ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Control Group ◽  
Intermittent Fasting ◽  
High Fat ◽  
Hepatic Lipid Accumulation ◽  
Density Lipoprotein Receptor ◽  
Chemokine Ligand ◽  
Atherosclerosis Treatment

Atherosclerosis is a major pathology for cardiovascular diseases (CVDs). Clinically, the intermittent fasting (IF) has been observed to reduce the risk of CVDs. However, the effect of IF on the development of atherosclerosis has not been fully elucidated. Herein, we determined the protection of IF against high-fat diet–induced atherosclerosis in pro-atherogenic low-density lipoprotein receptor deficient (LDLR-/-) mice and the potentially involved mechanisms. The LDLR-/- mice were scheduled intermittent fasting cycles of 3-day HFD feeding ad libitum and 1 day fasting, while the mice in the control group were continuously fed HFD. The treatment was lasted for 7 weeks (∼12 cycles) or 14 weeks (∼24 cycles). Associated with the reduced total HFD intake, IF substantially reduced lesions in the en face aorta and aortic root sinus. It also increased plaque stability by increasing the smooth muscle cell (SMC)/collagen content and fibrotic cap thickness while reducing macrophage accumulation and necrotic core areas. Mechanistically, IF reduced serum total and LDL cholesterol levels by inhibiting cholesterol synthesis in the liver. Meanwhile, HFD-induced hepatic lipid accumulation was attenuated by IF. Interestingly, circulating Ly6Chigh monocytes but not T cells and serum c-c motif chemokine ligand 2 levels were significantly reduced by IF. Functionally, adhesion of monocytes to the aortic endothelium was decreased by IF via inhibiting VCAM-1 and ICAM-1 expression. Taken together, our study indicates that IF reduces atherosclerosis in LDLR-/- mice by reducing monocyte chemoattraction/adhesion and ameliorating hypercholesterolemia and suggests its potential application for atherosclerosis treatment.

Cholesterol Levels In Patients With Newly Diagnosed Chronic Lymphocytic Leukemia: A retrospective Multicenter Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5292-5292
Author(s):  
Irfan Yavasoglu ◽  
Gokhan Pektas ◽  
Fergün Yilmaz ◽  
Gülsüm Akgün ◽  
Anil Tombak ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lymphocytic Leukemia ◽  
Lipoprotein Cholesterol ◽  
Control Group ◽  
Low Density Lipoprotein Cholesterol ◽  
Cholesterol Levels ◽  
Lipid Parameters ◽  
Low Cholesterol ◽  
Retrospective Multicenter Study

Abstract Low cholesterol levels can be detected in solid tumors and hematological malignancies such as muliple myeloma. Moreover chloesterol levels reduced in some experimental studies of patients with chronic lymphocytic leukemia (CLL). In this retrospective multicenter study, lipid levels were retrospectively evaluated in 420 (264 male and 256 female with mean age 64 ± 11 years) patients with newly diagnosed CLL, according to the International CLL study group. 71 (28 male and 43 female with mean age 55 ± 9 years) healthy subjects as control group were included to this study. Lipid parameters such as total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), very low-density lipoprotein-cholesterol (VLDL-C), and triglyceride levels were measured with enzymatic/ calorimetric method and Architect C800 instrument. Low-density lipoprotein-cholesterol (LDL-C) levels were calculated according to Friedwald formula. Lipid parameters between two groups were compared with Mann-Whitney U test. A value of p< 0.05 was accepted as statistically significant. According to Binet classification, 60% of patients were in stage A, while 25% of them were in stage C. In CLL patients, the levels of TC, HDL-C, and LDL-C were lower than those of control group (p=0.001). There was no significantly difference for triglyceride and VLDL-C levels between two groups (p>0.05) (Table-1). The levels of TC, LDL-C, and HDL-C in the patients with stage C were lower than those of both stage A and stage B (Table-2). Low cholesterol levels in patients with CLL may occur due to increased use of cholesterol by lymphocytes.Table-1Lipid parameters in control group and CLL patientsCLL (N:420)Control (N:71)P valueTC (mg/dl)175±41217±36<0.001HDL-C (mg/dl)37±1153±14<0.001LDL-C (mg/dl)108±30131±29<0.001Triglyceride (mg/dl)140±71147±68>0.05VLDL-C (mg/dl)31±1731±17>0.05Table 2Lipid parameters in the patients according to Binet classificationStage A (n:255)Stage B(n:61)Stage C(n:104)P valueTC(mg/dl)183±38179±43156±40<0.001HDL-C(mg/dl)40±1237±1232±12<0.001LDL-C (mg/dl)112±28110±3398±30<0.001Triglyceride (mg/dl)141±76136±53141±68>0.05VLDL-C(mg/dl)30±1535±3331±13>0.05 Disclosures: Sonmez: Novartis Pharmaceuticals Corporation, Turkey: Membership on an entity’s Board of Directors or advisory committees.

scholarly journals Bioactive Compounds of Porcine Hearts and Aortas May Improve Cardiovascular Disorders in Humans

2021 ◽  
Vol 18 (14) ◽  
pp. 7330
Author(s):  
Irina Chernukha ◽  
Elena Kotenkova ◽  
Svetlana Derbeneva ◽  
Daniil Khvostov
Keyword(s):  
Bioactive Compounds ◽  
Biological Effects ◽  
Low Density Lipoprotein ◽  
Meat Product ◽  
Density Lipoprotein ◽  
Supportive Therapy ◽  
Control Group ◽  
Cholesterol Levels ◽  
Calorie Diet ◽  
The Difference

Functional foods promote health benefits in human metabolism, with bioactive compounds acting as therapeutic agents. The aim was to investigate the biological effects of a pâté made of pork hearts and aortas, minced, sterilised and packed in tins. Adults (61–66 years old) with a body mass index of 26.4–60.7 kg/m2 (n = 36) were randomly divided into two groups: one group consumed a low-calorie diet (LCD), while the other consumed an LCD with the developed meat product (MP) for 28–30 days. Serum biochemical parameters, anthropometry and blood pressure were measured. Consumption of an LCD + MP by experimental group participants helped to maintain reduced cholesterol levels. The difference in total cholesterol was significantly different (p = 0.018) from that of the control group, mainly due to the difference in low-density lipoprotein cholesterol (p = 0.005). Six peptides with potential cholesterol-binding properties and four peptides with potential antioxidant activity were identified in the MP, while elevation of the content of two peptides with potential angiotensin-converting enzyme-inhibitory activity was detected in patients’ plasma. Intervention with the MP can be considered as a supportive therapy to the main treatment for medical cardiovascular diseases due to a positive effect on serum cholesterol.

scholarly journals Thymoquinone Protects Neurons in the Cerebellum of Rats through Mitigating Oxidative Stress and Inflammation Following High-Fat Diet Supplementation

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 165
Author(s):  
Aziza Alrafiah
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
High Fat Diet ◽  
Neuronal Damage ◽  
Morphological Changes ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
The Body ◽  
Control Group ◽  
High Fat

High-fat diet (HFD) is a major problem causing neuronal damage. Thymoquinone (TQ) could regulate oxidative stress and the inflammatory process. Hence, the present study elucidated the significant role of TQ on oxidative stress, inflammation, as well as morphological changes in the cerebellum of rats with HFD. Rats were divided into three groups as (1) control, (2) saturated HFD for eight weeks and (3) HFD supplementation (four weeks) followed by TQ 300 mg/kg/day treated (four weeks). After treatment, blood samples were collected to measure oxidative stress markers glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and inflammatory cytokines. Furthermore, neuronal morphological changes were also observed in the cerebellum of the rats. HFD rats show higher body weight (286.5 ± 7.4 g) as compared with the control group (224.67 ± 1.78 g). TQ treatment significantly (p < 0.05) lowered the body weight (225.83 ± 13.15 g). TQ produced a significant (p < 0.05) reduction in cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL). The antioxidative enzymes significantly reduced in HFD rats (GSH, 1.46 ± 0.36 mol/L and SOD, 99.13 ± 5.41 µmol/mL) as compared with the control group (GSH, 6.25 ± 0.36 mol/L and SOD, 159.67 ± 10.67 µmol/mL). MDA was increased significantly in HFD rats (2.05 ± 0.25 nmol/L) compared to the control group (0.695 ± 0.11 nmol/L). Surprisingly, treatment with TQ could improve the level of GSH, MDA, and SOD. TQ treatment significantly (p < 0.05) reduced the inflammatory markers as compared with HFD alone. TQ treatment minimizes neuronal damage as well as reduces inflammation and improves antioxidant enzymes. TQ can be considered as a promising agent in preventing the neuronal morphological changes in the cerebellum of obese populations.

scholarly journals Effect of atorvastatin on spermatogenesis in rats: A stereological study

2021 ◽  
Vol 19 (12) ◽  
pp. 2609-2614
Author(s):  
Ekrem Akdeniz ◽  
Mehmet Emin Onger ◽  
Mustafa Suat Bolat ◽  
Fatih Firat ◽  
Metin Gur ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Study Groups ◽  
Lipoprotein Cholesterol ◽  
Control Group ◽  
Total Testosterone ◽  
Cholesterol Levels ◽  
Significant Difference ◽  
Optical Fractionator ◽  
Rat Spermatogenesis

Purpose: To investigate the effects of oral atorvastatin on spermatogenesis in a rat model.Methods: Rats were equally assigned into control and study groups, the latter receiving atorvastatin (20 mg/kg/day). At the end of 12 weeks, spermatogenetic activity was evaluated using stereological and optical fractionator methods. Serum follicle-stimulating hormone (FSH), total testosterone (TT), and luteinizing hormone (LH) levels were measured using micro–ELISA kits. Total cholesterol, triglyceride (TG), low-density lipoprotein cholesterol (LDL - C), and high-density lipoprotein cholesterol levels were also measured by enzymatic colorimetric assays.Results: Testicular stereological analysis revealed that atorvastatin reduced Sertoli cell numbers (p < 0.001), spermatogonia (p < 0.001), spermatocytes (p < 0.001), and seminiferous tubule diameters (p < 0.001). LDL – C (p = 0.01) and TG (p = 0.01) values were significantly lower in the study group compared with the control group. There was no significant difference in FSH (p = 0.44), LH (p = 0.48),and TT (p = 0.06) levels between the groups.Conclusion: The findings show that atorvastatin causes deleterious effects on rat spermatogenesis. It should therefore be used with caution in clinical practice owing to its potential adverse effects, especially on male fertility. Keywords: Statin, Atorvastatin, Spermatogenesis, Stereology, Testis

scholarly journals PENGARUH KADAR TRIGLISERIDA TERHADAP KEKAKUAN ARTERI PADA MODEL HEWAN TIKUS WISTAR JANTAN

2020 ◽  
Vol 7 (2) ◽  
pp. 102
Author(s):  
Patonah Hasimun ◽  
Hasballah Zakaria
Keyword(s):  
Cardiovascular Disease ◽  
Heart Rate ◽  
Arterial Stiffness ◽  
High Fat Diet ◽  
Pulse Wave ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Triglyceride ◽  
Positive Control ◽  
Control Group

<p align="center"><strong>ABSTRAK</strong></p><p> </p><p>Hasil studi epidemiologi diketahui bahwa trigliserida merupakan salah satu factor resiko independent terjadinya penyakit kardiovaskular walaupun target kadar <em>low density lipoprotein</em> (LDL) telah tercapai dengan obat statin. Diduga terdapat hubungan antara kadar trigliserida dengan elastisitas arteri. Kekakuan arteri telah diakui berkaitan erat dengan penyakit kardiovaskular. Penelitian ini bertujuan untuk mengetahui efek hipertrigliseridemia terhadap tingkat kekakuan arteri pada model hewan tikus Wistar yang diinduksi pakan tinggi lemak dan fruktosa 25%. Sejumlah 10 ekor tikus dikelompokkan secara acak menjadi 2 kelompok terdiri dari kelompok control normal menerima pakan normal dan kelompok control positif menerima pakan tinggi lemak dan air minum fruktosa 25% selama 28 hari. Pengukuran <em>pulse wave velocity</em> (PWV), denyut jantung, dan kadar trigliserida serum dilakukan pada hari ke 28. Hasil menunjukkan, kelompok kontrol positif mengalami kenaikan kadar trigliserida serum yang disertai dengan meningkatnya nilai PWV dan denyut jantung yang menunjukkan terjadinya kekakuan arteri yang berbeda bermakna secara statistik terhadap kelompok kontrol normal (p&lt;0.05). Hasil dapat disimpulkan bahwa terdapat hubungan positif antara kadar trigliserida dengan kekakuan arteri. Semakin tinggi kadar trigliserida meningkatkan kekakuan arteri sehingga resiko kardiovaskular semakin meningkat.</p><p> </p><p><strong>Kata kunc</strong>i : trigliserida, kekakuan arteri, denyut jantung, kardiovaskular</p><p> </p><p> </p><p> </p><p align="center"><strong><em>ABSTRACT</em></strong></p><p> </p><p><em>Epidemiological studies report that triglycerides are an independent risk factor for cardiovascular disease even though the target level of low density lipoprotein (LDL) has been achieved with statin drugs. It is suspected that there is a relationship between triglyceride levels and arterial elasticity. Arterial stiffness has been recognized as being closely related to cardiovascular disease. This study aims to determine the effect of hypertriglyceridemia on arterial stiffness in animal models of Wistar rats induced by a high-fat diet and 25% fructose in drinking water. A total of 10 rats were randomly divided into 2 groups consisting of a normal control group receiving normal feed and a positive control group receiving a high-fat diet and 25% fructose in drinking water for 28 days. Measurements of pulse wave velocity (PWV), heart rate, and serum triglyceride levels were carried out on day 28. The positive control group experienced an increase in serum triglyceride levels accompanied by an increase in PWV and heart rate that was statistically significantly different (p &lt;0.05) compared to the group normal. The results concluded that there was a positive relationship between triglyceride levels and arterial stiffness. Higher triglyceride levels increase arterial stiffness. it increases the risk of cardiovascular disease.</em></p><p><em> </em></p><p><strong><em>Keywords</em></strong><strong><em> </em></strong><em>: triglyceride, arterial stiffness, </em><em>heart rate, cardiovascular</em><em> </em></p>

Plasma Lipid and Lipoprotein Abnormalities in Patients with Malabsorption

1973 ◽  
Vol 45 (5) ◽  
pp. 583-592 ◽  
Author(s):  
Gilbert R. Thompson ◽  
J. Paul Miller
Keyword(s):  
Plasma Lipids ◽  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Serum Triglyceride ◽  
Plasma Lipoproteins ◽  
Low Density ◽  
Cholesterol Levels ◽  
Lipids And Lipoproteins

1. Plasma lipids and lipoproteins have been studied in control subjects and patients with various types of steatorrhoea. 2. Low plasma cholesterol levels were found in malabsorbers and were associated with decreased amounts of low-density lipoprotein (LDL) in males and high-density lipoprotein (HDL) in females. 3. Serum triglyceride levels were normal in males, but exceeded control values in some of the females, due to an increase in very-low-density lipoprotein. 4. LDL composition was abnormal in both male and female malabsorbers, with a decreased proportion of cholesterol ester and an increased proportion of triglyceride. There was also an increased proportion of triglyceride in HDL. 5. These findings show that malabsorption markedly influences not only the concentration but also the composition of plasma lipoproteins.

scholarly journals Dietary Cholesterol Is Highly Associated with Severity of Hyperlipidemia and Atherosclerotic Lesions in Heterozygous LDLR-Deficient Hamsters

2019 ◽  
Vol 20 (14) ◽  
pp. 3515 ◽  
Author(s):  
Jinjie Wang ◽  
Kunxiang He ◽  
Chun Yang ◽  
Xiao Lin ◽  
Xin Zhang ◽  
...  
Keyword(s):  
Coronary Arteries ◽  
Plasma Lipids ◽  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Dietary Cholesterol ◽  
Gene Mutations ◽  
Density Lipoprotein ◽  
Inherited Disease ◽  
Atherosclerotic Lesions ◽  
Cholesterol Levels

Objective: Familial hypercholesterolemia (FH) is a dominant inherited disease caused mainly by low-density lipoprotein receptor (LDLR) gene mutations. To different extents, both heterozygous and homozygous FH patients develop premature coronary heart disease (CHD). However, most of the experimental animal models with LDLR deficiency could not fully recapitulate FH because they develop hyperlipidemia and atherosclerosis only in homozygous, but not in heterozygous, form. In the current study, we investigated the responsiveness of the LDLR+/− hamster to dietary cholesterol and whether plasma cholesterol levels were positively associated with the severity of atherosclerosis. Approach and Methods: wild type WT and LDLR+/− hamsters were fed a high fat diet with different cholesterol contents (HCHF) for 12 or 16 weeks. Plasma lipids, (apo)lipoproteins, and atherosclerosis in both the aorta and coronary arteries were analyzed. After a HCHF diet challenge, the levels of total cholesterol (TC) in WT and LDLR+/− hamsters were significantly elevated, but the latter showed a more pronounced lipoprotein profile, with higher cholesterol levels that were positively correlated with dietary cholesterol contents. The LDLR+/− hamsters also showed accelerated atherosclerotic lesions in the aorta and coronary arteries, whereas only mild aortic lesions were observed in WT hamsters. Conclusions: Our findings demonstrate that, unlike other rodent animals, the levels of plasma cholesterol in hamsters can be significantly modulated by the intervention of dietary cholesterol, which were closely associated with severity of atherosclerosis in LDLR+/− hamsters, suggesting that the LDLR+/− hamster is an ideal animal model for FH and has great potential in the study of FH and atherosclerosis-related CHD.

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