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  • Ovid Technologies (Wolters Kluwer Health)  (7)
  • 1
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    Abstract 593: High-Monounsaturated Fat Mediterranean-Type Diet Reduces Foamy Monocyte Formation and Atherosclerosis in Ldlr-/- Mice on High-Cholesterol Diet
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 37, No. suppl_1 ( 2017-05)
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 37, No. suppl_1 ( 2017-05)
    Abstract: A large randomized clinical trial (PREDIMED) showed that adding “healthy monounsaturated fat (MUF)” to Mediterranean diet (MedD) by supplementation with extra virgin olive oil or nuts led to a reduction in atherosclerotic cardiovascular events, but the mechanisms remain incompletely understood. Hyperlipidemia, a major risk factor for atherosclerosis, may induce lipid accumulation in circulating monocytes, leading to formation of foamy monocytes (FMs), which contribute to atherosclerosis. We hypothesize that high-MUF MedD reduces FM formation and therefore inhibits atherogenesis associated with hyperlipidemia. To test this, LDLR-/- mice were fed western-type high-saturated fat, high-cholesterol diet (WD) (21% milkfat containing 13.3% saturated fat and 5.9% MUF; 0.2% cholesterol), high-MUF MedD with high cholesterol (HC-MedD, 21% fat [from extra-virgin olive oil, walnuts, almonds, and hazelnuts] containing 2.6% saturated fat and 13.4% MUF; 0.2% cholesterol), or normal diet (ND, control). At 3 months, mice on HC-MedD had similar body weight gain but significantly lower liver/body weight index compared to mice on WD. Plasma triglyceride levels were significantly lower in mice on HC-MedD (318 ± 31 mg/dL, n=13) than on WD (769 ± 60 mg/dL, n=9, P 〈 0.05 vs HC-MedD group). Total cholesterol levels tended to be lower in mice on HC-MedD (2088 ± 180 mg/dL) than on WD (3092 ± 220 mg/dL). Compared to mice on WD, mice on HC-MedD had lower proportions of FMs and lower side scatter values (491 ± 11 vs 555 ± 3 in WD group, n=10/group, P 〈 0.001), indicating less lipid, in FMs. Lipid accumulation in FMs of LDLR-/- on WD accelerated conversion of monocyte subsets from CD11c-CD36+ to CD11c+CD36+, leading to increased ratio of CD11c+CD36+ to CD11c-CD36+ monocytes in mice on WD (2.6 ± 0.3, n=10) vs ND (1.3 ± 0.2, n=9, P 〈 0.01). In contrast, this ratio was not increased in mice on HC-MedD (1.4 ± 0.1, n=10) compared to mice on ND, and was lower than that in mice on WD (P 〈 0.01). Oil red O staining of en face aorta showed 27% decrease in lesion areas in mice on HC-MedD vs on WD (P 〈 0.05). In summary, compared to WD high in saturated fat and cholesterol, high-MUF MedD with high cholesterol lowered triglyceride levels, inhibited FM formation, and reduced atherosclerotic lesion size in LDLR-/- mice.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/atvb.37.suppl_1.593
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
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  • 2
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    Abstract 598: Monounsaturated Fat Reduces Foamy Monocyte Formation and Atherosclerosis Development in Ldlr -/- Mice Compared to Western High Saturated Fat Diet
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 38, No. Suppl_1 ( 2018-05)
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 38, No. Suppl_1 ( 2018-05)
    Abstract: Monounsaturated fat (MUF)-rich Mediterranean-type diet (MedD) has been reported to improve atherosclerotic outcome in clinical studies, but the underlying mechanism is ill defined. Circulating foamy monocytes (FMs, monocytes with intracellular lipid droplets), which are CD11c + and highly adherent to inflamed endothelium, contribute to atherosclerosis development. In the present study, we investigated the influence of MedD on FM formation and its contribution to atherosclerosis in mice. LDLR -/- mice were fed MedD with high cholesterol (MedD [w/w, 21% total fat from olive oil and nut] containing 2.6% saturated fat and 13.4% MUF; 0.2% cholesterol) or western diet (WD, 21% milkfat-containing 13.3% saturated fat and 5.9% MUF; 0.2% cholesterol), with normal diet (ND) as control. Lesion area of the whole aorta examined by oil red staining at 3 months was significantly reduced in mice on MedD, compared to WD. Although plasma triglyceride levels were lower in mice on MedD than on WD, the free fatty acid profile indicated that MUFs concentration in plasma significantly increased in mice on MedD. Further, FMs from mice on MedD circulated at lower proportions and exhibited lower side scatter (SSC) than WD, indicating less lipid accumulation. Lipid accumulation in FMs from mice on WD accelerated their conversion from CD11c - /CD36 + to CD11c + /CD36 + compared to mice on ND. In contrast, this accelerated conversion did not occur in mice on MedD. Compared to WD, MedD reduced the number of firmly arrested CD11c + monocytes on vascular cell adhesion molecule-1 and E-selectin coated coverslips detected in an ex-vivo shear flow assay. Similarly, fewer CD11c + macrophages were observed in the lesion of aortic sinus in mice on MedD than on WD. In summary, compared to WD high in saturated fat and cholesterol, MedD high in MUF and cholesterol lowered triglyceride levels, inhibited foamy monocyte formation and adhesion, and reduced atherosclerosis in LDLR -/- mice.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/atvb.38.suppl_1.598
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
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  • 3
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    Abstract 562: Foamy Monocytes in Hypertriglyceridemia
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 38, No. Suppl_1 ( 2018-05)
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 38, No. Suppl_1 ( 2018-05)
    Abstract: Objective: Hypertriglyceridemia (HTG) increases risk for atherosclerotic cardiovascular disease, but the mechanisms remain poorly defined. Foamy monocytes are lipid-loaded monocytes in circulation that contribute to atherosclerosis under hypercholesterolemia. Human study has proved that HTG is associated with formation of foamy monocytes. Our study is to examine formation of foamy monocytes in HTG and their potential contribution to atherosclerosis in mouse models. Approach and results: In vivo mouse models of HTG included wild-type C57BL/6 mice on high fat diet (HFD) injected intraperitoneally with LPL inhibitor, Poloxamer 407 (P407, 0.25mg/g, every two days), as a chemically-induced model and mice with transgenic overexpression of human ApoCIII (ApoCIIItg) as a genetic model. Based on CD11c and CD36, monocytes were identified as CD36 - CD11c - , CD36 + CD11c - and CD36 + CD11c + subsets. In the first model, at 24h of the first injection, triglyceride levels increased to 367 ±84 mg/dL, higher than that of control group with saline injection (60 ±22 mg/dL, n=4, P 〈 0.001). Meanwhile, the side scatter (SSC, representing cell granularity) values and Nile red staining for lipids of CD36 + CD11c + monocytes increased significantly, indicating formation of foamy monocytes, in mice with HTG. Furthermore, CD11c mean fluorescence intensity of CD36 + CD11c + foamy monocytes increased significantly at 2 weeks of P407 injection. In ApoCIIItg mice fed HFD (5 weeks), the percentage and SSC value of CD36 + CD11c + monocytes increased significantly (37%±5%, 247±8), also indicating elevated granularity and lipid accumulation of these monocytes, compared to wild-type mice (26%±3%, p 〈 0.05; 226±8, p 〈 0.05, n=4-6). In vitro treatment with human triglyceride-rich lipoprotein (hTGRL) for 24h increased the granularity and Nile red staining intensity of THP-1 monocytes, indicating foamy monocyte formation. hTGRL treatment also increased THP-1 monocyte expression of CD36, with greater uptake of cholesteryl ester-rich lipoprotein. Conclusion: High triglyceride promotes foamy monocyte formation and induces monocyte phenotypic changes in mice and tissue culture, with increased expression of CD11c and CD36, which may contribute to development of atherosclerosis under HTG.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/atvb.38.suppl_1.562
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
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  • 4
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    Abstract 458: A Study Of Short-term Low-saturated Fat Versus High-saturated Fat Diet In Atherothrombosis Risk Factors In Subjects With Hypertriglyceridemia
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 43, No. Suppl_1 ( 2023-05)
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 43, No. Suppl_1 ( 2023-05)
    Abstract: Introduction: Dietary fat and composition may impact the risk of atherosclerotic cardiovascular disease (ASCVD) in subjects with hypertriglyceridemia (HTG). Hypothesis: We hypothesized that a low-saturated fat diet (LSFD), in contrast to a high-saturated fat diet (HSFD), improves blood lipid levels and reduces atherothrombosis risk factors in subjects with HTG. Method: Subjects with HTG and metabolic syndrome (n=19) were randomly placed on an LSFD (~25% of calories from fat, 5% from saturated fat) or an HSFD (~52% of calories from fat, 25% from saturated fat) for 4 days (day 1-4) and a breakfast on day 5 and then switched to the other diet after a 4- to 6-week washout period. Blood was collected on day 1 fasting before the start of the diet and on day 5 fasting and at 4 and 6 hours after breakfast. Lipid profiles and flow cytometry to measure monocyte intracellular lipid accumulation, monocyte expression of tissue factor (TF), and monocyte-platelet aggregates (MPAs) were performed. Results: On day 5, LSFD, compared to HSFD, induced lower plasma levels of postprandial total triglyceride and LDL-triglyceride and fasting and postprandial total cholesterol, non-HDL-cholesterol, LDL-cholesterol, and small dense LDL-cholesterol. Classical and intermediate monocytes with LSFD, in contrast to HSFD, exhibited reduced intracellular lipid accumulation indicated by decreases in cellular granularity and nile red staining examined by flow cytometry. LSFD vs. HSFD also reduced classical monocyte uptake of oxidized LDL ex vivo at 4 hours postprandially on day 5. Surface level of TF was higher on classical and intermediate monocytes than on nonclassical monocytes assessed by mean fluorescence intensity. Classical and intermediate monocytes, compared to nonclassical monocytes, were also more prone to form aggregates with platelets. However, there was no significant difference between LSFD and HSFD in TF levels on any monocyte subsets and in MPAs of any monocyte subsets at any time points recorded. Conclusion: In subjects with HTG and metabolic syndrome, short-term LSFD, in contrast to HSFD, reduced monocyte lipid accumulation and oxidized LDL uptake but did not induce significant differences in monocyte surface levels of TF and MPA formation.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/atvb.43.suppl_1.458
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 5
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    Abstract 13285: Short-term Low-saturated Fat Diet Compared to High-saturated Fat Diet Improves Monocyte Phenotypes in Subjects With Hypertriglyceridemia
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Vol. 142, No. Suppl_3 ( 2020-11-17)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. Suppl_3 ( 2020-11-17)
    Abstract: Introduction: Clinical trials suggest that low-saturated fat diet (LSFD) may reduce the risk of atherosclerotic cardiovascular disease (ASCVD) in subjects with hypertriglyceridemia (HTG). Monocytes play crucial roles in atherogenesis. Hypothesis: LSFD vs high-saturated fat diet (HSFD) improves monocyte phenotypes, thereby reducing ASCVD risk, in subjects with HTG. Methods: Subjects with HTG and metabolic syndrome (MetS, n=19) received isocaloric LSFD (~25% of calories from fat, 5% from saturated fat) and HSFD (~52% of calories from fat, 25% from saturated fat) in randomized order for 4 days (days 1-4) plus a breakfast on day 5, separated by a 4- to 6-week washout period. Blood was drawn on day 1 fasting before the diets and 3 times on day 5 (fasting before the breakfast and 4 and 6 hours postprandial) for measurement of lipid profile and analyses of monocyte phenotypes by flow cytometry and monocyte adhesion by a lab-on-a-chip microfluidic assay. Results: On day 5, LSFD, compared to HSFD, induced lower plasma levels of postprandial total triglyceride and LDL-triglyceride and fasting and postprandial total cholesterol, LDL-cholesterol, and small dense LDL-cholesterol. Compared to HSFD, LSFD reduced fasting and postprandial intracellular lipid accumulation in classical and intermediate monocytes examined by nile red staining and indicated by side scatter value of flow cytometric analysis. LSFD versus HSFD also reduced ex vivo uptake of oxidized LDL by classical monocytes at 4 hours postprandially and by intermediate monocytes in fasting state. Surface levels of molecules involved in monocyte adhesion/migration, including CD11c, CD81, and CCR2, were lower on monocytes with LSFD than with HSFD. Consistently, LSFD compared to HSFD reduced monocyte adhesion to VCAM-1. Intracellular levels of cytokines such as IL-1β, TNFα, and IL-6 in monocytes showed no difference between the two diets. Conclusions: In subjects with HTG and MetS, short-term LSFD compared to HSFD reduces monocyte intracellular lipid accumulation and improves monocyte phenotypes with reductions in monocyte adhesion and oxidized LDL uptake. These findings highlight the importance of diet composition in monocyte phenotypes and possibly atherosclerosis risks in patients with HTG and MetS.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.142.suppl_3.13285
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 6
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    Abstract 11296: Short-Term Low-Saturated Fat Diet Compared to High-Saturated Fat Diet in Patients with Hypertriglyceridemia: Lipids and Lipoproteins Associated with Monocyte Phenotypic Changes
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation Vol. 144, No. Suppl_1 ( 2021-11-16)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 144, No. Suppl_1 ( 2021-11-16)
    Abstract: Background: Monocyte phenotypic changes play a pivotal role in atherogenesis and can be induced by plasma lipids. We analyzed associations of monocyte phenotypes with lipid profiles and the potential of predicting monocyte phenotypes by lipid variables in subjects with hypertriglyceridemia (HTG) after short-term intake of low-saturated fat diet (LSFD) and high-saturated fat diet (HSFD). Method: Subjects with HTG (n=19, 10 men and 9 women, aged 53.9±13.7 years) received isocaloric LSFD (~25% of calories from fat, 5% from saturated fat) and HSFD (~52% of calories from fat, 25% from saturated fat) in randomized order for 4 days (days 1-4) and a test meal on day 5, separated by a 4- to 6-week washout period. Blood was taken on day 1 fasting before the diets and on day 5 fasting and 4 and 6 hours after the test meal to examine lipoprotein profile by enzymatic assay, fatty acids by nuclear magnetic resonance spectroscopy, and monocyte phenotypes by flow cytometry. Least absolute shrinkage and selection operator (LASSO) regression models were built to identify influential lipid variables for key monocyte markers that responded differently to the two diets. Results: LSFD, compared to HSFD, induced lower plasma levels of postprandial total triglyceride (TG), VLDL-TG, and LDL-TG and fasting and postprandial total cholesterol and LDL-cholesterol and altered fatty acid composition, with reduced saturated fatty acids (SFAs) but increased polyunsaturated fatty acids (PUFAs). Compared to HSFD, LSFD reduced monocyte lipid accumulation and levels of several surface markers involved in monocyte adhesion and migration including CD11c, a β2 integrin, on intermediate monocytes. Using the LASSO regression models, we identified that total cholesterol, LDL-TG, and apoB were positively correlated and n-3 PUFAs negatively correlated with lipid accumulation in intermediate monocytes and that total TG, LDL-TG, and apoCIII were positively correlated with CD11c levels on intermediate monocytes. Conclusions: In subjects with HTG, short-term LSFD compared to HSFD improves lipid profiles and monocyte phenotypes. We also identified specific plasma lipid parameters that may be reliable predictors for and contribute to specific monocyte phenotypic changes in HTG.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.144.suppl_1.11296
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 7
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    Replacing Saturated Fat With Unsaturated Fat in Western Diet Reduces Foamy Monocytes and Atherosclerosis in Male Ldlr –/– Mice
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 40, No. 1 ( 2020-01), p. 72-85
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 40, No. 1 ( 2020-01), p. 72-85
    Abstract: A Mediterranean diet supplemented with olive oil and nuts prevents cardiovascular disease in clinical studies, but the underlying mechanisms are incompletely understood. We investigated whether the preventive effect of the diet could be due to inhibition of atherosclerosis and foamy monocyte formation in Ldlr –/– mice fed with a diet in which milkfat in a Western diet (WD) was replaced with extra-virgin olive oil and nuts (EVOND). Approach and Results: Ldlr –/– mice were fed EVOND or a Western diet for 3 (or 6) months. Compared with the Western diet, EVOND decreased triglyceride and cholesterol levels but increased unsaturated fatty acid concentrations in plasma. EVOND also lowered intracellular lipid accumulation in circulating monocytes, indicating less formation of foamy monocytes, compared with the Western diet. In addition, compared with the Western diet, EVOND reduced monocyte expression of inflammatory cytokines, CD36, and CD11c, with decreased monocyte uptake of oxLDL (oxidized LDL [low-density lipoprotein]) ex vivo and reduced CD11c + foamy monocyte firm arrest on vascular cell adhesion molecule-1 and E-selectin–coated slides in an ex vivo shear flow assay. Along with these changes, EVOND compared with the Western diet reduced the number of CD11c + macrophages in atherosclerotic lesions and lowered atherosclerotic lesion area of the whole aorta and aortic sinus. Conclusions: A diet enriched in extra-virgin olive oil and nuts, compared with a Western diet high in saturated fat, lowered plasma cholesterol and triglyceride levels, inhibited foamy monocyte formation, inflammation, and adhesion, and reduced atherosclerosis in Ldlr –/– mice.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/ATVBAHA.119.313078
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1494427-3
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