Statins: protection against heart attacks and strokes—hallelujah!

Hallelujah Moments ◽

10.1093/oso/9780190080457.003.0005 ◽

2020 ◽

pp. 61-84

Author(s):

Eugene H. Cordes

Keyword(s):

Soil Sample ◽

Metabolic Pathway ◽

Fermentation Broth ◽

Plasma Cholesterol ◽

Golf Course ◽

Drug Candidate ◽

Cholesterol Lowering ◽

Heart Attacks ◽

Cholesterol Levels ◽

The World

The class of drugs known as statins is very effective in lowering plasma cholesterol levels; these drugs have been established to reduce the frequency of heart attacks and strokes in multiple settings. The statins are inhibitors of an enzyme known as HMGR, an enzyme on the metabolic pathway to cholesterol. The first statin, mevastatin, was discovered by Japanese scientists in a fermentation broth from an organism cultured from a soil sample taken near a golf course. Mevastatin established the efficacy of HMGR inhibitors as cholesterol-lowering agents but ultimately failed as a drug candidate. The first marketed statin was lovastatin (Mevacor), isolated at Merck from a fermentation broth. Pravachol followed from Squibb, as did simvastatin (Zocor) from Merck and subsequently several other, notably Lipitor and Crestor. They are among the most widely prescribed drugs in the world.

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Lipid-lowering Activity of Natural and Semi-Synthetic Sterols and Stanols

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j3gc84 ◽

2015 ◽

Vol 18 (4) ◽

pp. 344 ◽

Cited By ~ 8

Author(s):

Dhiaa A Taha ◽

Ellen K Wasan ◽

Kishor M Wasan ◽

Pavel Gershkovich

Keyword(s):

Ascorbic Acid ◽

Animal Studies ◽

Molecular Mechanisms ◽

Plasma Cholesterol ◽

Plant Sterols ◽

Water Soluble ◽

Lipid Lowering ◽

Cholesterol Lowering ◽

Cholesterol Levels ◽

Lowering Activity

Consumption of plant sterols/ stanols has long been demonstrated to reduce plasma cholesterol levels. The objective of this review is to demonstrate the lipid-lowering activity and anti-atherogenic effects of natural and semi-synthetic plant sterols/ stanols based on evidence from cell-culture studies, animal studies and clinical trials. Additionally, this review highlights certain molecular mechanisms by which plant sterols/ stanols lower plasma cholesterol levels with a special emphasis on factors that affect the cholesterol-lowering activity of plant sterols/stanols. The crystalline nature and the poor oil solubility of these natural products could be important factors that limit their cholesterol-lowering efficiency. Several attempts have been made to improve the cholesterol-lowering activity by enhancing the bioavailability of crystalline sterols and stanols. Approaches involved reduction of the crystal size and/or esterification with fatty acids from vegetable or fish oils. However, the most promising approach in this context is the chemical modification of plant sterols /stanols into water soluble disodium ascorbyl phytostanyl phosphates analogue by esterification with ascorbic acid. This novel semi-synthetic stanol derivative has improved efficacy over natural plant sterols/ stanols and can provide additional benefits by combining the cholesterol-lowering properties of plant stanols with the antioxidant potential of ascorbic acid. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Co-repressing immunometabolic processes in atherosclerosis

Cardiovascular Medicine ◽

10.4414/cvm.2021.w10043 ◽

2021 ◽

Author(s):

Sokrates Stein

Keyword(s):

Nuclear Receptor ◽

Plasma Cholesterol ◽

Interacting Protein ◽

Receptor Signalling ◽

Cholesterol Levels ◽

The Metabolic Syndrome ◽

The World ◽

Obesity Hypertension ◽

Metabolic Dysfunctions ◽

Insight Into

Cardiovascular disease is the primary cause of mortality in the world, and tightly associated with the metabolic syndrome, which is a cluster of interconnected metabolic dysfunctions including insulin resistance, obesity, hypertension and dyslipidaemias. These dysfunctions increase the risk of developing atherosclerosis and consequent cardiovascular diseases, such as myocardial infarction and stroke. Atherosclerosis is primarily triggered by increased plasma cholesterol levels and can be classified as an immunometabolic disease, a chronic disease that is affected by both metabolic and inflammatory triggers and/or mediators. These triggers and mediators activate common downstream pathways, including nuclear receptor signalling. Interestingly, specific cofactors that bind to these complexes act as immunometabolic integrators. This review provides examples of such co-regulator complexes, including nuclear sirtuins, nuclear receptor co-repressor 1 (NCOR1), nuclear receptor interacting protein 1 (NRIP1), and prospero homeobox 1 (PROX1). Their study might provide novel insight into mechanistic regulations and the identification of new targets to treat atherosclerosis.

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Management of Hypercholesterolemia Through Dietary ß-glucans–Insights From a Zebrafish Model

Frontiers in Nutrition ◽

10.3389/fnut.2021.797452 ◽

2022 ◽

Vol 8 ◽

Author(s):

Adnan Hussain Gora ◽

Saima Rehman ◽

Viswanath Kiron ◽

Jorge Dias ◽

Jorge M. O. Fernandes ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Plasma Cholesterol ◽

Cholesterol Biosynthesis ◽

Dietary Cholesterol ◽

Blood Cholesterol ◽

Control Group ◽

Zebrafish Model ◽

Cholesterol Lowering ◽

Cholesterol Levels ◽

Transcriptomic Changes

Consumption of lipid-rich foods can increase the blood cholesterol content. β-glucans have hypocholesterolemic effect. However, subtle changes in their molecular branching can influence bioactivity. Therefore, a comparative investigation of the cholesterol-lowering potential of two β-glucans with different branching patterns and a cholesterol-lowering drug, namely simvastatin was undertaken employing the zebrafish (Danio rerio) model of diet-induced hypercholesterolemia. Fish were allocated to 5 dietary treatments; a control group, a high cholesterol group, two β-glucan groups, and a simvastatin group. We investigated plasma total cholesterol, LDL and HDL cholesterol levels, histological changes in the tissues, and explored intestinal transcriptomic changes induced by the experimental diets. Dietary cholesterol likely caused the suppression of endogenous cholesterol biosynthesis, induced dysfunction of endoplasmic reticulum and mitochondria, and altered the histomorphology of the intestine. The two β-glucans and simvastatin significantly abated the rise in plasma cholesterol levels and restored the expression of specific genes to alleviate the endoplasmic reticulum-related effects induced by the dietary cholesterol. Furthermore, the distinct patterns of transcriptomic changes in the intestine elicited by the oat and microalga β-glucans impacted processes such as fatty acid metabolism, protein catabolic processes, and nuclear division. Oat and microalgal β-glucans also altered the pattern of lipid deposition in the liver. Our study provides insights into the effectiveness of different β-glucans to alleviate dysfunctions in lipid metabolism caused by dietary cholesterol.

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Plasma cholesterol levels in free-ranging macaques compared with captive macaques and humans

Primates ◽

10.1007/bf02557599 ◽

2000 ◽

Vol 41 (3) ◽

pp. 299-309 ◽

Cited By ~ 8

Author(s):

Akiko Takenaka ◽

Yuko Matsumoto ◽

Aika Nagaya ◽

Kunio Watanabe ◽

Shunji Goto ◽

...

Keyword(s):

Plasma Cholesterol ◽

Cholesterol Levels ◽

Free Ranging

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Hyodeoxycholic acid efficiently suppresses atherosclerosis formation and plasma cholesterol levels in mice

The Journal of Lipid Research ◽

10.1016/s0022-2275(20)31575-3 ◽

2001 ◽

Vol 42 (8) ◽

pp. 1250-1256 ◽

Cited By ~ 1

Author(s):

Ephraim Sehayek ◽

Jennie G. Ono ◽

Elizabeth M. Duncan ◽

Ashok K. Batta ◽

Gerald Salen ◽

...

Keyword(s):

Plasma Cholesterol ◽

Cholesterol Levels ◽

Hyodeoxycholic Acid

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Plasma cholesterol lowering action of bile acid binding polymers in experimental animals

The Journal of Lipid Research ◽

10.1016/s0022-2275(20)41235-0 ◽

1960 ◽

Vol 1 (5) ◽

pp. 469-473 ◽

Cited By ~ 1

Author(s):

DavidM. Tennent ◽

Henry Siegel ◽

MaryE. Zanetti ◽

GuntherW. Kuron ◽

WaltherH. Ott ◽

...

Keyword(s):

Bile Acid ◽

Plasma Cholesterol ◽

Cholesterol Lowering ◽

Experimental Animals ◽

Bile Acid Binding

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Targeting the Cholesterol Paradigm in the Risk Reduction for Atherosclerotic Cardiovascular Disease: Does the Mechanism of Action of Pharmacotherapy Matter for Clinical Outcomes?

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/10742484211023632 ◽

2021 ◽

pp. 107424842110236

Author(s):

Ruihai Zhou ◽

George A. Stouffer ◽

Sidney C. Smith

Keyword(s):

Cardiovascular Disease ◽

Clinical Outcomes ◽

Mechanism Of Action ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Blood Cholesterol ◽

Atherosclerotic Cardiovascular Disease ◽

Pcsk9 Inhibitors ◽

Cholesterol Lowering ◽

Cholesterol Levels

Hypercholesterolemia is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD). Low-density lipoprotein cholesterol (LDL-C) has been labeled as “bad” cholesterol and high-density lipoprotein cholesterol (HDL-C) as “good” cholesterol. The prevailing hypothesis is that lowering blood cholesterol levels, especially LDL-C, reduces vascular deposition and retention of cholesterol or apolipoprotein B (apoB)-containing lipoproteins which are atherogenic. We review herein the clinical trial data on different pharmacological approaches to lowering blood cholesterol and propose that the mechanism of action of cholesterol lowering, as well as the amplitude of cholesterol reduction, are critically important in leading to improved clinical outcomes in ASCVD. The effects of bile acid sequestrants, fibrates, niacin, cholesteryl ester transfer protein (CETP) inhibitors, apolipoprotein A-I and HDL mimetics, apoB regulators, acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitors, cholesterol absorption inhibitors, statins, and proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors, among other strategies are reviewed. Clinical evidence supports that different classes of cholesterol lowering or lipoprotein regulating approaches yielded variable effects on ASCVD outcomes, especially in cardiovascular and all-cause mortality. Statins are the most widely used cholesterol lowering agents and have the best proven cardiovascular event and survival benefits. Manipulating cholesterol levels by specific targeting of apoproteins or lipoproteins has not yielded clinical benefit. Understanding why lowering LDL-C by different approaches varies in clinical outcomes of ASCVD, especially in survival benefit, may shed further light on our evolving understanding of how cholesterol and its carrier lipoproteins are involved in ASCVD and aid in developing effective pharmacological strategies to improve the clinical outcomes of ASCVD.

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Gestational Diabetes Mellitus Treatment Schemes Modify Maternal Plasma Cholesterol Levels Dependent to Women´s Weight: Possible Impact on Feto-Placental Vascular Function

Nutrients ◽

10.3390/nu12020506 ◽

2020 ◽

Vol 12 (2) ◽

pp. 506 ◽

Cited By ~ 1

Author(s):

Susana Contreras-Duarte ◽

Lorena Carvajal ◽

María Jesús Garchitorena ◽

Mario Subiabre ◽

Bárbara Fuenzalida ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Vascular Function ◽

Plasma Cholesterol ◽

Umbilical Vein ◽

Maternal Plasma ◽

Maternal Weight ◽

Cholesterol Levels ◽

The Impact

Gestational diabetes mellitus (GDM) associates with fetal endothelial dysfunction (ED), which occurs independently of adequate glycemic control. Scarce information exists about the impact of different GDM therapeutic schemes on maternal dyslipidemia and obesity and their contribution to the development of fetal-ED. The aim of this study was to evaluate the effect of GDM-treatments on lipid levels in nonobese (N) and obese (O) pregnant women and the effect of maternal cholesterol levels in GDM-associated ED in the umbilical vein (UV). O-GDM women treated with diet showed decreased total cholesterol (TC) and low-density lipoproteins (LDL) levels with respect to N-GDM ones. Moreover, O-GDM women treated with diet in addition to insulin showed higher TC and LDL levels than N-GDM women. The maximum relaxation to calcitonin gene-related peptide of the UV rings was lower in the N-GDM group compared to the N one, and increased maternal levels of TC were associated with even lower dilation in the N-GDM group. We conclude that GDM-treatments modulate the TC and LDL levels depending on maternal weight. Additionally, increased TC levels worsen the GDM-associated ED of UV rings. This study suggests that it could be relevant to consider a specific GDM-treatment according to weight in order to prevent fetal-ED, as well as to consider the possible effects of maternal lipids during pregnancy.

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