Dietary Cholesterol, Serum Lipids, and Heart Disease: Are Eggs Working for or Against You?

Objective: Coronary heart disease and diabetes are highly prevalent among obese populations due to aberrant dietary cholesterol metabolism. Here we investigated the effect of heat shock factor-1 (HSF-1) on atherosclerosis and dietary cholesterol metabolism. Methods and Results: Atherogenic western diet-induced weight gain was reduced in HSF-1 and LDLr double knock out mice (HSF-1 -/- /LDLr -/- ), compared to LDLr -/- mice. Atherosclerotic lesion growth in aortic arch and carotid regions was retarded. Also, repression of PPAR-γ2 and AMPKα expression in adipose tissue, low hepatic steatosis, and lessened plasma adiponectins and lipoproteins were observed. Furthermore, reduced heat shock proteins and their mRNA levels in atherosclerotic lesions correlated with reduction in lesion burden. In HSF-1 -/- /LDLr -/- liver, higher cholesterol 7α hydroxylase (CYP7A1, the rate limiting enzyme in the synthesis of bile acid from cholesterol) and MDR1/p-glycoprotein (bile salt transporter across the hepatocyte canalicular membrane) gene expressions were observed, consistent with higher bile acid sequestration and larger hepatic bile ducts. HSF-1 deletion, however, upregulated both CYP7A1 enzyme and MDR1/p-glycoportein expression and activities, due to removal of its repressive binding in the CYP7A1 and MDR1 gene promoters. This increased the conversion of cholesterol into 7-α-hydroxycholesterol and bile acid, and dietary cholesterol metabolism. Conclusions: HSF-1 ablation not only eliminates heat shock response to retard atherosclerosis, but it also transcriptionally upregulates CYP7A1 and MDR1/P-gp axis to increase cholesterol metabolism. Therefore, HSF-1 is a metabolic regulator of dietary cholesterol and a major contributor to heart disease among obese population.

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THE EFFECT OF CERTAIN THYROXINE ANALOGUES ON THE SERUM LIPIDS IN HUMAN SUBJECTS

Journal of Endocrinology ◽

10.1677/joe.0.0210033 ◽

1960 ◽

Vol 21 (1) ◽

pp. 33-43 ◽

Cited By ~ 46

Author(s):

G. S. BOYD ◽

M. F. OLIVER

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Basal Metabolic Rate ◽

Serum Lipids ◽

Myocardial Metabolism ◽

Human Subjects ◽

Cholesterol Levels ◽

Oxygen Requirements ◽

Low Cholesterol ◽

Hypothyroid Patients

SUMMARY 1. Certain analogues of thyroxine have been administered to twenty-six hypothyroid patients and 132 euthyroid hypercholesterolaemic men with coronary heart disease. The analogues studied were d-thyroxine, 3:5:3′:5′-tetraiodothyroformic acid, 3:5:3′:5′-tetraiodothyronamine, 3:5:3′-triiodo-l-thyronine, 3:5:3′-triiodo-d-thyronine, 3:5:3′-triiodothyroacetic acid, 3:5-diiodo-l-thyronine, 3:5-diiodo-d-thyronine and 3:5-diiodothyroacetic acid. 2. In both hypothyroid and euthyroid patients, most of these analogues reduced the serum cholesterol without necessarily elevating the basal metabolic rate (b.m.r.). Nevertheless, in euthyroid patients with coronary heart disease several produced angina in the absence of any change in b.m.r. and this has been regarded as a sign of increased myocardial metabolism insufficient to be reflected in the overall measure of b.m.r. of all tissues. The possible differential effect of these analogues on the oxygen requirements of various tissues is discussed. 3. Although it has been possible to maintain low cholesterol levels for periods up to 3 months during the administration of several of these analogues, the dose required for this purpose was often so close to the dose which provoked angina that most cannot be recommended for widespread administration for the reduction of the hypercholesterolaemia frequently found in patients who have coronary heart disease. d-Thyroxine may prove to be an exception and requires further clinical assessment.

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Interaction of dietary fat intake and omega-3 fatty acids, on platelet aggregation, haemostatic variables and serum lipids, in men at risk of heart disease

Prostaglandins Leukotrienes and Essential Fatty Acids ◽

10.1016/s0952-3278(97)90452-x ◽

1997 ◽

Vol 57 (4-5) ◽

pp. 518

Keyword(s):

At Risk ◽

Fatty Acids ◽

Heart Disease ◽

Platelet Aggregation ◽

Dietary Fat ◽

Serum Lipids ◽

Fat Intake ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

Dietary Fat Intake

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Abstract P266: Change in the Association Between Serum Lipids and Coronary Heart Disease among Middle-Aged Adults: Observational Data from the Pre- and Post-Statin Era.

Circulation ◽

10.1161/circ.129.suppl_1.p266 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Lisandro D Colantonio ◽

Vera Bittner ◽

Emily B Levitan ◽

Shia Kent ◽

Monika M Safford ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Racial Differences ◽

Serum Lipids ◽

Current Analysis ◽

Middle Aged ◽

Chd Risk Factors ◽

Middle Aged Adults ◽

Study Participants ◽

Statin Use

Dyslipidemia is a major risk factor for coronary heart disease (CHD) and is usually treated with statins. Few observational studies have examined associations between lipids and CHD in the era of widespread statin use. The objective of the current analysis was to contrast the association between serum lipids and incident coronary heart disease (CHD) among middle-aged adults before and after statin use became widespread. Methods: We analyzed data from 14,590 Atherosclerosis Risk In Communities (ARIC) study participants who were recruited in 1987-1989 (pre-statins), and 13,196 REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants (9,578 not taking statins) who were recruited in 2003-2007 (post-statins). Our analysis was restricted to participants 45 to 64 years of age without a history of CHD at baseline. Total and HDL cholesterol (HDL-C) and fasting triglycerides (TG) were measured at baseline and used to calculate LDL-C, non-HDL-C, total-to-HDL-C ratio and total-to-TG ratio. Each lipid parameter was categorized into four levels based on REGARDS quartile cut-points. Results: In ARIC, participants with higher LDL-C were more likely to have diabetes and use antihypertensive medication, whereas these CHD risk factors were progressively less common at higher LDL-C in REGARDS participants not taking statins. Over a maximum 7 years of follow up, 513 and 278 incident CHD events occurred among ARIC and REGARDS participants, respectively. After multivariable adjustment, higher categories of each lipid marker (lower categories of HDL-C) were associated with a higher hazard ratio (HR) for CHD among ARIC participants, but not among REGARDS participants not taking statins (figure). No association between lipid markers and CHD was observed among REGARDS participants taking statins. DISCUSION: The current analysis suggests that the widespread preferential use of statins among high risk individuals may have obscured the association between lipids and incident CHD.

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Serum Lipids Profiling Perturbances in Patients with Ischemic Heart Disease and Ischemic Cardiomyopathy

10.21203/rs.2.19569/v3 ◽

2020 ◽

Author(s):

Lin Yang ◽

Liang Wang ◽

Yangyang Deng ◽

Lizhe Sun ◽

Bowen Low ◽

...

Keyword(s):

Heart Disease ◽

Ischemic Heart Disease ◽

Ischemic Cardiomyopathy ◽

Serum Lipids ◽

Ischemic Heart ◽

Negative Ion ◽

Serum Samples ◽

Cross Sectional ◽

Negative Ion Mode ◽

Positive Ion

Abstract Background: Ischemic heart disease (IHD) is a common cardiovascular disorder associated with inadequate blood supply to the myocardium. Chronic coronary ischemia leads to ischemic cardiomyopathy (ICM). Despite their rising prevalence and morbidity, few studies have discussed the lipids alterations in these patients. Methods: In this cross-sectional study, we analyzed serum lipids profile in IHD and ICM patients using a lipidomics approach. Consecutive consenting patients admitted to the hospital for IHD and ICM were enrolled. Serum samples were obtained after overnight fasting. Non-targeted metabolomics was applied to demonstrate lipids metabolic profile in control, IHD and ICM patients. Results: A total of 63 and 62 lipids were detected in negative and positive ion mode respectively. Among them, 16:0 Lyso PI, 18:1 Lyso PI in negative ion mode, and 19:0 Lyso PC, 12:0 SM d18:1/12:0, 15:0 Lyso PC, 17:0 PC, 18:1-18:0 PC in positive ion mode were significantly altered both in IHD and ICM as compared to control. 13:0 Lyso PI, 18:0 Lyso PI, 16:0 PE, 14:0 PC DMPC, 16:0 ceramide, 18:0 ceramide in negative ion mode, and 17:0 PE, 19:0 PC, 14:0 Lyso PC, 20:0 Lyso PC, 18:0 PC DSPC, 18:0-22:6 PC in positive ion mode were significantly altered only in ICM as compared to IHD and control. Conclusion: Using non-targeted lipidomics profiling, we have successfully identified a group of circulating lipids that were significantly altered in IHD and ICM. The lipids metabolic signatures shed light on potential new biomarkers and therapeutics for preventing and treating ICM.

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