Ovariectomy in rats and high dietary cholesterol intake combine to decrease gene expression of molecular marker of VLDL synthesis

The development of inexpensive and effective approaches to transiently decrease gene expression in vivo would be useful for the study of physiological processes in living animals. DNAzymes are a novel class of DNA oligonucleotides that can catalytically cleave target mRNAs and thereby reduce protein production. However, current methods for their delivery in vivo are limited and inefficient. In this study, we show that electroporation can be used to deliver DNAzymes to the intact mesenteric vasculature of rats. With the use of PKC-ϵ as a target, a set of wild-type and mutant control DNAzymes was designed and shown to reduce both PKC-ϵ mRNA and protein levels in cultured smooth muscle cells in a specific manner. The wild-type DNAzyme reduced PKC-ϵ protein levels by 70% at 24 h in two different cell lines without decreasing the levels of the five other PKC isoforms tested. When delivered to the intact vasculature using electroporation, the DNAzyme reduced PKC-ϵ protein levels by >60% without affecting these other PKC isoforms. Electroporation was required for oligonucleotide transfer and was able to deliver the DNAzymes to multiple cell layers in the vessel wall. Protein levels were reduced maximally by 24 h postelectroporation and returned to normal by 48 h. These results suggest that electroporation can be used to deliver DNAzymes and other DNA oligonucleotides to the vasculature in vivo and can decrease gene expression for a window of time that can be used for experimental studies.

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Dietary cholesterol and egg intake in relation to incident cardiovascular disease and all-cause and cause-specific mortality in postmenopausal women

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqaa353 ◽

2020 ◽

Author(s):

Guo-Chong Chen ◽

Li-Hua Chen ◽

Yasmin Mossavar-Rahmani ◽

Victor Kamensky ◽

Aladdin H Shadyab ◽

...

Keyword(s):

Cardiovascular Disease ◽

Postmenopausal Women ◽

Dietary Cholesterol ◽

Saturated Fat ◽

Inverse Association ◽

Egg Consumption ◽

All Cause Mortality ◽

Specific Mortality ◽

Cholesterol Intake ◽

Incident Cardiovascular Disease

ABSTRACT Background The potential cardiovascular impact of dietary cholesterol intake has been actively debated for decades. Objectives We aimed to evaluate associations of dietary cholesterol and egg intakes with incident cardiovascular disease (CVD) and all-cause and cause-specific mortality. Methods We included 96,831 US postmenopausal women aged 50–79 y without known CVD or cancer during baseline enrollment (1993–1998) of the Women's Health Initiative. Dietary information was collected using a validated FFQ. Incident CVD [i.e., ischemic heart disease (IHD) and stroke] and all-cause and cause-specific mortality were ascertained and adjudicated through February 2018. Results A total of 9808 incident CVD cases and 19,508 all-cause deaths occurred during a median follow-up of 17.8 y and 18.9 y, respectively. After multivariable adjustment for traditional risk factors and key dietary nutrients including dietary saturated fat, there were modest associations of dietary cholesterol intake with incident CVD (HRQ5versusQ1: 1.12; 95% CI: 1.03, 1.21; P-trend < 0.001) and all-cause mortality (HRQ5versusQ1: 1.09; 95% CI: 1.02, 1.15; P-trend < 0.001). Significant positive associations were also observed between dietary cholesterol and incident IHD (P-trend = 0.007), incident ischemic stroke (P-trend = 0.002), and CVD mortality (P-trend = 0.002), whereas there was an inverse association for incident hemorrhagic stroke (P-trend = 0.037) and no association for mortality from cancer, Alzheimer disease/dementia, respiratory diseases, or other causes (P-trend > 0.05). Higher egg consumption was also associated with modestly higher risk of incident CVD (P-trend = 0.004) and all-cause mortality (P-trend < 0.001), with HRs of 1.14 (95% CI: 1.04, 1.25) and 1.14 (95% CI: 1.07, 1.22), respectively, when comparing ≥1 egg/d with <1 egg/wk. Conclusions Both higher dietary cholesterol intake and higher egg consumption appeared to be associated with modestly elevated risk of incident CVD and all-cause mortality in US postmenopausal women.

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Association between Dietary Cholesterol and Their Food Sources and Risk for Hypercholesterolemia: The 2012–2016 Korea National Health and Nutrition Examination Survey

Nutrients ◽

10.3390/nu11040846 ◽

2019 ◽

Vol 11 (4) ◽

pp. 846 ◽

Cited By ~ 9

Author(s):

Dongjoo Cha ◽

Yongsoon Park

Keyword(s):

Low Density Lipoprotein ◽

Dietary Cholesterol ◽

Density Lipoprotein ◽

Serum Levels ◽

Food Sources ◽

Direct Effects ◽

Low Density Lipoprotein Cholesterol ◽

Processed Meats ◽

Health And Nutrition ◽

Cholesterol Intake

It remains unclear whether cholesterol intake can increase serum cholesterol. Therefore, the present study aimed to investigate the hypothesis that the risk for hypercholesterolemia was not associated with intake of dietary cholesterol after adjusting for saturated fatty acid (SFA). Based on the data from the 2012–2016 KNHANES, dietary cholesterol was positively associated with the risk for abnormalities in total cholesterol (TC) (odds ratio (OR): 1.153, 95% confidence interval (CI): 0.995–1.337; p = 0.028) and low-density lipoprotein cholesterol (LDL-C) (OR: 1.186, 95% CI: 1.019–1.382; p = 0.018) levels before adjusting for SFA; after adjusting for SFA, no significant associations were found between these variables. The mediation analysis showed that dietary cholesterol had no direct effects on the serum levels of TC and LDL-C; in contrast, SFA had significant indirect effects on the association between dietary cholesterol and serum levels of TC and LDL-C. Furthermore, processed meats, but not eggs and other meats, were positively associated with the risk for abnormalities in both TC (OR: 1.220, 95% CI: 1.083–1.374; p = 0.001) and LDL-C (OR: 1.193, 95% CI: 1.052–1.354; p = 0.004) levels. The present study suggested that higher intake of processed meats with high SFA, but not dietary cholesterol was associated with higher risk for abnormalities in TC and LDL-C levels.

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Genetic susceptibility, dietary cholesterol intake, and plasma cholesterol levels in a Chinese population

The Journal of Lipid Research ◽

10.1194/jlr.ra120001009 ◽

2020 ◽

Vol 61 (11) ◽

pp. 1504-1511

Author(s):

Shaofeng Huo ◽

Liang Sun ◽

Geng Zong ◽

Boyu Song ◽

He Zheng ◽

...

Keyword(s):

Genetic Susceptibility ◽

Chinese Population ◽

Plasma Cholesterol ◽

Nutrition Transition ◽

Dietary Cholesterol ◽

Effect Sizes ◽

Risk Scores ◽

Asian Countries ◽

Cholesterol Levels ◽

Cholesterol Intake

Accompanied with nutrition transition, non-HDL-C levels of individuals in Asian countries has increased rapidly, which has caused the global epicenter of nonoptimal cholesterol to shift from Western countries to Asian countries. Thus, it is critical to underline major genetic and dietary determinants. In the current study of 2,330 Chinese individuals, genetic risk scores (GRSs) were calculated for total cholesterol (TC; GRSTC, 57 SNPs), LDL-C (GRSLDL-C, 45 SNPs), and HDL-C (GRSHDL-C, 65 SNPs) based on SNPs from the Global Lipid Genetics Consortium study. Cholesterol intake was estimated by a 74-item food-frequency questionnaire. Associations of dietary cholesterol intake with plasma TC and LDL-C strengthened across quartiles of the GRSTC (effect sizes: −0.29, 0.34, 2.45, and 6.47; Pinteraction = 0.002) and GRSLDL-C (effect sizes: −1.35, 0.17, 5.45, and 6.07; Pinteraction = 0.001), respectively. Similar interactions with non-HDL-C were observed between dietary cholesterol and GRSTC (Pinteraction = 0.001) and GRSLDL-C (Pinteraction = 0.004). The adverse effects of GRSTC on TC (effect sizes across dietary cholesterol quartiles: 0.51, 0.82, 1.21, and 1.31; Pinteraction = 0.023) and GRSLDL-C on LDL-C (effect sizes across dietary cholesterol quartiles: 0.66, 0.52, 1.12, and 1.56; Pinteraction = 0.020) were more profound in those having higher cholesterol intake compared with those with lower intake. Our findings suggest significant interactions between genetic susceptibility and dietary cholesterol intake on plasma cholesterol profiles in a Chinese population.

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