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Questions and Answers
What is the primary consequence of low levels of HDL cholesterol?
What is the primary consequence of low levels of HDL cholesterol?
What characteristic helps to differentiate circulating lipoproteins from one another?
What characteristic helps to differentiate circulating lipoproteins from one another?
Familial Hypercholesterolemia primarily results from defects in which type of receptor?
Familial Hypercholesterolemia primarily results from defects in which type of receptor?
Which type of particles primarily transport triglycerides and cholesterol in the blood?
Which type of particles primarily transport triglycerides and cholesterol in the blood?
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What is a common approach to managing hyperlipidemia?
What is a common approach to managing hyperlipidemia?
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What role does cholesterol acyltransferase (ACAT) play in cholesterol metabolism?
What role does cholesterol acyltransferase (ACAT) play in cholesterol metabolism?
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How do drugs that selectively inhibit cholesterol absorption affect hepatic cholesterol levels?
How do drugs that selectively inhibit cholesterol absorption affect hepatic cholesterol levels?
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What happens to LDL receptors when unesterified cholesterol levels increase in the cell?
What happens to LDL receptors when unesterified cholesterol levels increase in the cell?
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Which process occurs when LDL particles are not taken up by LDL receptors?
Which process occurs when LDL particles are not taken up by LDL receptors?
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What effect does oxidized LDL have on endothelial function?
What effect does oxidized LDL have on endothelial function?
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What is a consequence of excessive foam cell death in atherosclerosis?
What is a consequence of excessive foam cell death in atherosclerosis?
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Which of the following is a major risk factor for developing atherosclerosis?
Which of the following is a major risk factor for developing atherosclerosis?
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What triggers the formation of foam cells in the context of LDL metabolism?
What triggers the formation of foam cells in the context of LDL metabolism?
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What is the primary goal of cholesterol-lowering therapy?
What is the primary goal of cholesterol-lowering therapy?
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In cholesterol metabolism, which lipoprotein is most closely associated with atherosclerosis?
In cholesterol metabolism, which lipoprotein is most closely associated with atherosclerosis?
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Which of the following drugs is classified as an ACE inhibitor?
Which of the following drugs is classified as an ACE inhibitor?
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Familial hypercholesterolemia is primarily characterized by elevated levels of which lipoprotein?
Familial hypercholesterolemia is primarily characterized by elevated levels of which lipoprotein?
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What is the relationship between HDL levels and heart disease risk?
What is the relationship between HDL levels and heart disease risk?
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Which medication is most effective as a first line of defense against Type 2 Diabetes?
Which medication is most effective as a first line of defense against Type 2 Diabetes?
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Which statement is true regarding recent cholesterol treatment guidelines?
Which statement is true regarding recent cholesterol treatment guidelines?
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Which of the following drugs is classified as a statin?
Which of the following drugs is classified as a statin?
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Which type of drug is most effective for treating anxiety disorders?
Which type of drug is most effective for treating anxiety disorders?
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What is the main function of the LDL receptor in cholesterol metabolism?
What is the main function of the LDL receptor in cholesterol metabolism?
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What condition results from mutations in the LDL receptor gene that impair cholesterol metabolism?
What condition results from mutations in the LDL receptor gene that impair cholesterol metabolism?
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Which of the following describes a potential defect related to LDL receptor mutations in Familial Hypercholesterolemia?
Which of the following describes a potential defect related to LDL receptor mutations in Familial Hypercholesterolemia?
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What is the primary effect of intracellular unesterified cholesterol on cholesterol synthesis?
What is the primary effect of intracellular unesterified cholesterol on cholesterol synthesis?
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Which statement accurately describes the homozygous form of Familial Hypercholesterolemia?
Which statement accurately describes the homozygous form of Familial Hypercholesterolemia?
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How do VLDL particles contribute to cholesterol metabolism?
How do VLDL particles contribute to cholesterol metabolism?
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What clinical feature is associated with heterozygous Familial Hypercholesterolemia?
What clinical feature is associated with heterozygous Familial Hypercholesterolemia?
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What role do chylomicrons play in lipid metabolism?
What role do chylomicrons play in lipid metabolism?
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What is a consequence of defective LDL receptor function?
What is a consequence of defective LDL receptor function?
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Which of the following therapies targets LDL cholesterol in patients with hyperlipidemia?
Which of the following therapies targets LDL cholesterol in patients with hyperlipidemia?
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What is the most common prevalence of heterozygous Familial Hypercholesterolemia in the USA?
What is the most common prevalence of heterozygous Familial Hypercholesterolemia in the USA?
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Study Notes
Lecture #29: Hyperlipidemia Physiology
- Lecture was presented by Julia Hum, PhD
- Course meets Monday/Wednesday/Friday from 2:00-2:50pm
- Office hours are Monday/Wednesday/Friday from 11:00am-12:00pm (317B or WebEx)
- Course website: marian.edu/medicalschool
- Learning Objectives:
- Define causes and correlations of coronary heart disease (CHD) with cholesterol and triglyceride levels.
- Understand the basic biochemistry and physiology of cholesterol and lipoprotein metabolism.
- Understand the metabolism of ApoB-containing lipoproteins and their lifespan.
- Describe LDL particle formation and clearance, predicting changes with genetic mutations.
- List treatment goals for CHD.
- Calculate and interpret the 10-year ASCVD risk.
- Lecture relies on information from Principles of Pharmacology 3e (Baca, Golan, Ch. 19) and Lippincott Illustrated Reviews: Pharmacology 6e (Yellepeddi, Ch. 23).
L29: "Take Home" Slide
- Visual aids depict LDL binding to LDL receptors.
- Internalization and recycling of LDL receptors.
- Lysosome hydrolysis of cholesterol.
- Cholesterol movement to the endoplasmic reticulum (ER).
- HMGCoA reductase activity.
- ACAT activity.
- LDL receptor activity.
Case Study
- 42-year-old male with coronary artery disease, BMI 34, increased abdominal girth, and well-controlled hypertension.
- Ordered lipid panel:
- Total cholesterol
- LDL cholesterol
- HDL cholesterol
- Triglycerides
Coronary Heart Disease (CHD)
- CHD is a leading cause of death worldwide.
- CHD is correlated with high levels of LDL ("bad" cholesterol), high triglycerides, and low levels of HDL ("good" cholesterol).
Risk Factors for CHD/CAD
- This section is a title only, no specific details for the risk factors are presented
Coronary Heart Disease (CHD) continued
- Hyperlipidemias can result from an inherited defect in lipoprotein metabolism
- Appropriate lifestyle changes and drug therapy can significantly reduce CHD mortality.
- Antihyperlipidemic drugs are often taken long-term to control lipid levels.
Love for Lipids
- Essential for maintaining membrane integrity and biogenesis.
- Serve as energy sources, hormone precursors, and signaling molecules.
- Transport nonpolar lipids (e.g., triglycerides and cholesterol esters) in the blood via lipoproteins.
Biochemistry and Physiology of Cholesterol and Lipoprotein Metabolism
- Lipoproteins are macromolecular aggregates transporting triglycerides and cholesterol in the blood.
- Lipoproteins are differentiated by size, density, and protein content.
- Types of lipoproteins are listed along with their densities, diameters, and major lipid contents (cholesterol, triglycerides, phospholipids, in percentages).
Biochemistry and Physiology of Cholesterol and Lipoprotein Metabolism (cont.)
- Lipoproteins are microscopic particles ranging from 7-100nm in diameter.
- Consists of a monolayer of polar, amphipathic lipids surrounding a hydrophobic core.
- Apolipoproteins are amphipathic proteins that act as ligands for receptors, stabilize lipoprotein structure, and engage in biological functions.
- The hydrophobic core comprises primarily cholesteryl esters and triglycerides.
Biochemistry and Physiology of Cholesterol and Lipoprotein Metabolism (cont.)
- Lipoproteins are categorized by their function:
- delivery of triglycerides to muscle and fat tissue
- involved in cholesterol transport
- Examples of apoB containing lipoproteins- chylomicrons, VLDLs.
Metabolism of ApoB-Containing Lipoproteins
- Primary function of apoB-containing lipoproteins is to deliver fatty acids to muscle tissue for ATP biogenesis and adipose tissue for storage.
- Chylomicrons are formed in the intestine, transporting dietary triglycerides.
- VLDL particles are formed in the liver, transporting endogenously synthesized triglycerides.
Metabolism of ApoB-Containing Lipoproteins: Formation and Clearance of LDL Particles
- Unesterified cholesterol affects three major homeostatic pathways:
- Inhibits HMG-CoA reductase (inhibiting de novo cholesterol synthesis)
- Causes activation of ACAT (increasing esterification and storage of cholesterol)
Clinical Connection: Familial Hypercholesterolemia (FH) Type IIA
- Autosomal dominant disease causing defects in the LDL receptor.
- Four types of defects in LDL receptor: Synthesis, Membrane transport, Binding, internalization.
- Heterozygous individuals are affected in 1 in 500 people in the USA.
- Homozygous FH is a much rarer, more severe disorder (1 in 1 million in USA).
- Characterized by absence of functional LDL receptors.
Drugs for Hyperlipidemia
- Statins inhibit HMG-CoA reductase, reducing cholesterol synthesis in the cell.
- Ezetimibe selectively inhibits absorption of dietary and biliary cholesterol in the small intestine, decreasing cholesterol delivery to the liver, and reducing hepatic cholesterol stores.
Metabolism of ApoB-Containing Lipoproteins: Formation and Clearance of LDL Particles (cont.)
- LDL receptor expression is down-regulated by excess intracellular cholesterol.
- Hepatocytes are primarily responsible for removing LDL particles from the circulation.
LDL and Atherosclerosis
- LDL particles not taken up by LDL receptors migrate to the blood vessel's inner lining.
- Oxidation is a major factor in the formation of atherosclerotic lesions.
- Foam cell formation and death can lead to plaque rupture.
Oxidized LDL causes:
- Up-regulation of cytokine production
- Impaired endothelial function
- Increased expression of endothelial adhesion molecules
- Increase in local inflammatory response that promotes atherosclerosis.
Metabolism of ApoB-Containing Lipoproteins: Formation and Clearance of LDL Particles (cont.)
- Foam cells are a major component of atherosclerotic lesions;
- Excessive foam cell death destabilizes plaques.
- Plaque rupture is a key cause of acute ischemic cardiovascular events (e.g., heart attacks and strokes).
- High plasma LDL levels are a major risk factor for atherosclerosis and associated cardiovascular disease.
Top 10 List of Drugs Prescribed in America
- Provides a top 10 list of most prescribed medications, including their primary use.
Treatment Goals of Hypercholesterolemia
- Clinically important lipoproteins, in decreasing order of atherogenicity, are LDL, VLDL/chylomicrons, and HDL.
- High total cholesterol and elevated LDL are strongly associated with CHD occurrence.
- High HDL levels correlate to decreased risk of heart disease.
- Reduction of LDL levels is the primary goal of cholesterol-lowering therapy.
Treatment Goals of Hypercholesterolemia (cont.)
- Past cholesterol guidelines emphasized treating to specific target LDL levels.
- Newer guidelines now emphasize high-intensity or moderate-intensity statin therapy.
10-Year ASCVD Risk Estimator Plus
- Provides ASCVD risk categories from low to high.
- Provides online calculator link to calculate 10-year risk.
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Description
Explore the physiology of hyperlipidemia, focusing on cholesterol and triglyceride levels' impact on coronary heart disease (CHD). This quiz examines the biochemical processes of lipid metabolism and treatment goals for managing CHD. Enhance your understanding of lipoprotein interactions and cholesterol management strategies.
