L7 Lipid homeostasis and atherosclerosis Flashcards
What is dyslipidaemia and how is it related to cardiovascular disease (CVD)?
Dyslipidaemia refers to abnormal lipid levels in the blood, including raised total cholesterol, LDL cholesterol, or triglycerides, low HDL cholesterol, or a combination. It is a major risk factor for CVD, which includes heart attacks, strokes, and peripheral artery disease.
vWhat are the main types of dyslipidaemia?
The main types include hypercholesterolaemia (elevated LDL cholesterol), hypertriglyceridaemia (elevated triglycerides), and low HDL cholesterol. Mixed dyslipidaemia involves a combination of these abnormalities.
What is the role of LDL cholesterol in cardiovascular disease?
LDL cholesterol carries cholesterol to the arteries. Excess LDL can build up in artery walls, leading to plaque formation and atherosclerosis, increasing the risk of cardiovascular events like heart attacks and strokes.
Why is HDL cholesterol referred to as “good” cholesterol?
HDL cholesterol helps remove excess cholesterol from the blood and transports it to the liver for excretion, reducing the risk of atherosclerosis and cardiovascular disease.
What is the role of triglycerides in cardiovascular disease?
Elevated triglyceride levels can increase the size of lipid particles, contributing to plaque formation in arteries, which raises the risk of cardiovascular events.
What are the primary risk factors for dyslipidaemia and cardiovascular disease?
Key risk factors include genetic conditions (e.g., familial hypercholesterolaemia), dietary factors (high saturated fats), lifestyle factors (physical inactivity, smoking), obesity, and chronic conditions (e.g., diabetes, hypertension).
How is dietary fat absorbed in the body?
Dietary fat is broken down in the small intestine by lipases into free fatty acids (FFAs) and monoglycerides. These products are then incorporated into micelles, which facilitate their absorption into enterocytes (intestinal cells).
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How are lipids transported from enterocytes to the bloodstream?
Inside enterocytes, lipids are re-esterified into triglycerides and packaged with apolipoproteins into chylomicrons. These chylomicrons enter the lymphatic system, then the bloodstream.
How are lipids carried in the blood?
In the bloodstream, lipoproteins such as chylomicrons, VLDL, and HDL transport triglycerides and cholesterol to tissues for energy use or storage. Lipoproteins consist of lipids and apolipoproteins to ensure water solubility and effective transport.
What is the structure of bile salts (acids)?
Bile salts are amphipathic, meaning they have both hydrophilic (water-loving) and hydrophobic (water-hating) regions. This allows them to emulsify fats and aid in digestion.
What is the role of micelles in fat absorption?
Micelles are essential for the absorption of fat-soluble vitamins (A, D, E, and K). They transport the products of fat digestion to the surface of enterocytes for absorption.
What happens to bile salts after fat absorption?
After fat absorption, the micelle breaks down, and the bile salts can either return to the intestine for recycling or be reabsorbed into the bloodstream.
What is the role of glycerol in fat digestion?
Glycerol is a product of triglyceride breakdown and is absorbed into enterocytes where it can be re-esterified into triglycerides or used for energy.
How are bile salts recycled in the body?
Approximately 95% of bile salts are reabsorbed in the ileum, transported via the hepatic portal vein back to the liver, where they are recycled and re-secreted into new bile.
What happens to the remaining 5% of bile salts?
About 5% of bile salts are eliminated in faeces. The liver compensates for this loss by synthesising more bile salts from cholesterol.
Why might bile salts be a drug target?
Bile salts may be a drug target because they play a crucial role in lipid digestion and absorption. Targeting their recycling could help manage conditions related to cholesterol and fat metabolism.
How do bile salts aid in the absorption of dietary lipids?
Bile salts solubilise dietary lipids into micelles, allowing the lipids to pass through the diffusion barrier of the enterocytes for absorption.
What role does Niemann-Pick C1-like 1 (NPC1L1) protein play in lipid absorption?
NPC1L1 facilitates the uptake of cholesterol across the brush border membrane of enterocytes during lipid absorption.
Why might NPC1L1 be a drug target?
NPC1L1 could be a drug target because it is crucial in the absorption of cholesterol, and inhibiting it could help manage cholesterol levels and related conditions.
Where are chylomicrons formed and what is their primary function?
Chylomicrons are formed in enterocytes and are responsible for the uptake and transport of dietary lipids.
The main apolipoprotein component is ApoB48
What is the composition of chylomicrons?
Chylomicrons contain 85–92% triglycerides, 6–12% phospholipids, 1–3% cholesterol, and 1–2% proteins.
What happens to chylomicrons after they transport dietary lipids?
Chylomicron remnants are cleared by the liver after they have completed their lipid transport function.
What are apolipoproteins and what role do they play in lipid transport?
Apolipoproteins are amphipathic proteins that, together with phospholipids, bind lipids to form water-soluble lipoproteins and transport lipids and fat-soluble vitamins in blood, cerebrospinal fluid, and lymph.
In addition to being structural, what are some functions of apolipoproteins?
Apolipoproteins also act as ligands for lipoprotein receptors and activators/inhibitors of enzymes involved in the metabolism of lipoproteins.
What is the relationship between cholesterol and bile salts?
Cholesterol is a precursor for bile salts. The liver synthesizes bile salts from cholesterol to aid in the digestion and absorption of dietary fats. A small percentage of bile salts is lost in faeces, while the majority is recycled back to the liver through enterohepatic circulation.
How are bile salts important for fat digestion and absorption?
Bile salts are amphipathic and form micelles that solubilise dietary lipids, enabling them to pass through the enterocyte membrane. This allows for the efficient absorption of fat-soluble vitamins (A, D, E, K) and lipids from the digestive tract.
How is cholesterol related to hormones?
Cholesterol is the precursor for the synthesis of several important steroid hormones, including glucocorticoids (e.g., cortisol), mineralocorticoids (e.g., aldosterone), sex hormones (e.g., estrogen, testosterone), and vitamin D. These hormones are synthesised in the adrenal glands, gonads, and skin, respectively.
Where is cholesterol converted into steroid hormones?
Cholesterol is converted into steroid hormones primarily in the adrenal glands, gonads (ovaries and testes), and liver. This process involves enzymatic modifications to cholesterol’s structure, leading to the production of specific hormones.
How does serum cholesterol relate to cardiovascular health?
Serum cholesterol levels, especially low-density lipoprotein (LDL) cholesterol, are key indicators of cardiovascular health. Elevated LDL levels are associated with an increased risk of atherosclerosis, leading to the development of cardiovascular disease (CVD), including heart attacks and strokes.
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What is the role of HDL cholesterol in cardiovascular health?
High-density lipoprotein (HDL) cholesterol is considered “good” cholesterol because it helps to remove excess cholesterol from the bloodstream and transport it to the liver for excretion. Higher levels of HDL are associated with a reduced risk of cardiovascular disease.
What is the optimal range for serum cholesterol?
Total cholesterol should ideally be below 5.2 mmol/L (200 mg/dL). LDL cholesterol should be less than 3.0 mmol/L (100 mg/dL) for healthy individuals, while HDL cholesterol should ideally be above 1.0 mmol/L (40 mg/dL) in men and 1.3 mmol/L (50 mg/dL) in women.
How is LDL formed and what is its role?
Low-density lipoprotein (LDL) is formed from very-low-density lipoprotein (VLDL) as triglycerides are lost via lipoprotein lipase. LDL is primarily responsible for transporting cholesterol to peripheral tissues, and its cholesterol ester core contains 2/3 of the serum cholesterol content.
What is the clearance process for LDL?
LDL is cleared from circulation over 2-3 days. The liver removes LDL from the bloodstream through LDL receptors, which bind and endocytose LDL particles.
Why is LDL considered atherogenic?
LDL is considered atherogenic because elevated levels of LDL cholesterol in the blood can contribute to the formation of plaque in the arterial walls, leading to atherosclerosis and an increased risk of cardiovascular diseases such as heart attacks and strokes.
How does LDL cholesterol (LDL-C) bind to its receptor for clearance?
LDL-C binds to its receptor, LDL receptor (LDLR), through the apolipoprotein B-100 (ApoB-100) component of the LDL particle. This binding is crucial for the clearance of LDL particles from the blood.
What happens to the LDL receptor (LDLR) after it binds to LDL-C?
After LDLR binds to LDL-C, the receptor is internalised into the liver cell and then recycled back to the cell surface for future use in binding additional LDL particles.
What is the impact of mutations in the ApoB-100 gene?
Mutations in the ApoB-100 gene are associated with a significantly increased risk of atherosclerosis due to impaired LDL clearance, leading to elevated LDL-C levels and contributing to plaque formation in the arteries.
What is heterozygous familial hypercholesterolaemia (HeFH)?
Heterozygous familial hypercholesterolaemia (HeFH) is a genetic condition where individuals have one normal allele and one mutated allele for the LDL receptor gene, leading to partial reduction in LDL receptor activity and elevated LDL cholesterol (LDL-C) levels.
What is the effect of homozygous familial hypercholesterolaemia (HoFH) on LDL receptor activity?
Homozygous familial hypercholesterolaemia (HoFH) is a more severe form where individuals have two mutated alleles for the LDL receptor gene, resulting in nearly complete absence of LDL receptor activity, leading to very high LDL-C levels and a significantly increased risk of early cardiovascular disease.
How does familial hypercholesterolaemia (FH) affect LDL receptor activity?
n familial hypercholesterolaemia (FH), there is a deficiency or dysfunction of LDL receptors, leading to reduced clearance of LDL-C from the bloodstream and resulting in elevated cholesterol levels, contributing to early-onset atherosclerosis.
