Overview of the LDL receptor: relevance to cholesterol metabolism and future approaches for the treatment of coronary heart disease

Lagor, William R.; Millar, John S.

doi:10.2147/jrlcr.s6033

Cited by 9 publications

(9 citation statements)

References 114 publications

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“…This gene is exclusively expressed in the liver and contributes significantly to the uptake of fatty acids, and may lead to a build-up of triglycerides in the liver (61). Additionally, this study observed increases in Ldlr expression, a protein that transports low density lipoproteins into cells (62). Both genes are transcriptionally regulated by Ppara (63,64), which was also found to be increased in this study.…”

Section: Discussionsupporting

confidence: 73%

Chronic Atrazine Exposure Beginning Prenatally Impacts Liver Function and Sperm Concentration With Multi-Generational Consequences in Mice

2020

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Atrazine is a commonly used herbicide frequently detected in waterways and drinking water around the world. Worryingly, atrazine is an endocrine and metabolic disruptor but there is a lack of research regarding the effects of long-term exposure beginning in utero. In this study we investigated how chronic exposure to atrazine (5 mg/kg bw/day) in drinking water from E9.5 until 12 or 26 weeks of age affected metabolic and reproductive characteristics in male mice. We then examined whether mating these males to unexposed females altered in vitro embryo characteristics. Atrazine exposure caused a decrease in liver weight and changes in both liver and testis gene expression, specifically in genes involved in lipid uptake and fatty acid metabolism in the liver, as well as androgen conversion in the testis. Notably, atrazine exposure decreased epididymal sperm concentration and subsequent embryo cell numbers generated from the 12-week cohort males. Collectively, these data suggest that atrazine exposure, beginning prenatally, affects both metabolic and reproductive characteristics, and highlights the importance of assessing atrazine effects at different life stages and over multiple generations. The continued widespread use of atrazine warrants further studies, as it is essential to understand the health risks for all species, including humans.

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Section: Discussionsupporting

confidence: 73%

Chronic Atrazine Exposure Beginning Prenatally Impacts Liver Function and Sperm Concentration With Multi-Generational Consequences in Mice

2020

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“…This observed increase in LDL-R expression is frequently associated with the inhibition of cholesterol synthesis, accomplished by the suppression of HMG-CoA reductase. Consequently, this cascade stimulates the LDL-R pathway, augmenting the binding capacity of LDL-C to receptors on hepatocyte cell surfaces and ultimately lowering circulating LDL-C levels in the bloodstream 20 , In this context, it is proposed that Lnt may modulate HMG-CoA reductase by inducing LDL-R expression, thus constituting a significant mechanism in the reduction of LDL-C levels. Additionally, previous studies have reported the potent cholesterol-lowering activity of an ethanolic extract of Lnt leaves attributed to its inhibitory effect on HMG-CoA reductase and its favorable impact on lipid profile 36 .…”

Section: Impact Of Lnt Consumption On Blood Lipid Datamentioning

confidence: 99%

“…Studies have indicated that LDL-R internalizes LDL-C from plasma, releasing cholesterol into the cell, and appears pivotal in the feedback inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase 19 . Reduced LDL-R activity in the general population often contributes to hypercholesterolemia, fostering the development of atherosclerosis over time 20 . In the realm of biology, oxidative reactions can inflict damage on various cellular components, a phenomenon associated with aging and specific diseases, including cardiovascular diseases 11,12 .…”

Section: Introductionmentioning

confidence: 99%

Randomized, placebo-controlled pilot study investigating the effects of Laurus nobilis tea on lipid profiles and oxidative stress biomarkers in healthy North African volunteers

Chbili,

Mrad,

Graiet

et al. 2024

Nor. Afr. J. Food Nutr. Res.

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Background. Laurus-nobilis (Ln) is an evergreen tree from the Lauraceae family, widely utilized for its culinary and medicinal purposes. Aims. This study aims to investigate the effects of Ln-tea (Lnt) consumption on lipid profiles and oxidant/antioxidant stress biomarkers in healthy volunteers. Methods. A randomized, double-blind, placebo-controlled trial (PACTR202205671550114) was conducted involving healthy volunteers. Participants (n=62) were randomly assigned to either the experimental-group (EG, n=31), receiving Lnt, or the control-group (CG, n=31), receiving a placebo tea. The regimen was administered once daily for ten consecutive days. Blood samples were collected from each participant on two occasions: one day before the study (Day1) and one day after its completion (Day11). These samples underwent analysis for lipid data, including cholesterol, triglycerides, high- and low- density-lipoprotein-cholesterol (HDL-C, LDL-C, respectively), and low-density-lipoprotein-receptor (LDL-R). Additionally, oxidant/antioxidant stress biomarkers, such as superoxide-dismutase, uric-acid, and carbonylated-proteins, were assessed. Results. Data from seven participants (one from the EG, and six from the CG) were excluded from the final statistical analysis, resulting in 55 volunteers completing the study (30 in the EG, 25 in the CG). The two groups exhibited comparable demographic and clinical characteristics. In the EG, LDL-C decreased by 0.42 while HDL-C and LDL-R increased by 0.18 mmol/L and 189.45 pg/mL, respectively, compared to Day1. On Day11, the EG displayed lower LDL-C value and higher values of HDL-C and LDL-R compared to the CG. Significant interactive effects of the groups (2) vs. days (2) were observed for LDL-C, HDL-C, and LDL-R. No significant changes in oxidant/antioxidant stress biomarkers were noted between Day1 and Day11 in both groups. However, the EG showed higher levels of superoxide-dismutase compared to the CG on Day 11. Significant interactive effects of the groups (2) vs. days (2) were noted for superoxide-dismutase and carbonylated-proteins. Conclusions. Lnt infusion showed potential in modulating LDL-R activity levels, accompanied by elevated antioxidant activity. Keywords: Laurus, oxidative stress, plant extracts, therapeutic use, tea.

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“…Surprisingly, however, the results showed that despite the melatonin-mediated inhibition of cholesterol synthesis, the expression of LDL receptors, a crucial target in the process of extracellular cholesterol absorption, decreased [34]. It differs and opposes the action of melatonin from that typically revealed for statins in hepatocytes [35]. The binding affinity of LDL molecules to LDL receptors is not affected by melatonin [34].…”

Section: Melatonin As a Beneficial Regulator Of Cholesterol Metabomentioning

confidence: 99%

The Mystery behind the Pineal Gland: Melatonin Affects the Metabolism of Cholesterol

Karolczak

Watała

2019

Oxidative Medicine and Cellular Longevity

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Melatonin may be considered a cardioprotective agent. Since atherogenesis is partly associated with the metabolism of lipoproteins, it seems plausible that melatonin affects cardiovascular risk by modulating the metabolism of cholesterol and its subfractions. Moreover, cholesterol-driven atherogenesis can be hypothetically reduced by melatonin, mainly due to the minimalization of harmful reactions triggered in the cardiovascular system by the reactive oxygen species-induced toxic derivatives of cholesterol. In this review, we attempted to summarize the available data on the hypolipemizing effects of melatonin, with some emphasis on the molecular mechanisms underlying these reactions. We aimed to attract readers’ attention to the numerous gaps of knowledge present in the reviewed field and the essential irrelevance between the findings originating from different sources: clinical observations and in vitro mechanistic and molecular studies, as well as preclinical experiments involving animal models. Overall, such inconsistencies make it currently impossible to give a reliable opinion on the action of melatonin on the metabolism of lipoproteins.

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Overview of the LDL receptor: relevance to cholesterol metabolism and future approaches for the treatment of coronary heart disease

Cited by 9 publications

References 114 publications

Chronic Atrazine Exposure Beginning Prenatally Impacts Liver Function and Sperm Concentration With Multi-Generational Consequences in Mice

Chronic Atrazine Exposure Beginning Prenatally Impacts Liver Function and Sperm Concentration With Multi-Generational Consequences in Mice

Randomized, placebo-controlled pilot study investigating the effects of Laurus nobilis tea on lipid profiles and oxidative stress biomarkers in healthy North African volunteers

The Mystery behind the Pineal Gland: Melatonin Affects the Metabolism of Cholesterol

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