L7 Lipid homeostasis and atherosclerosis Flashcards
(100 cards)
1
Q
What is dyslipidaemia and how is it related to cardiovascular disease (CVD)?
A
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.
2
Q
vWhat are the main types of dyslipidaemia?
A
The main types include hypercholesterolaemia (elevated LDL cholesterol), hypertriglyceridaemia (elevated triglycerides), and low HDL cholesterol. Mixed dyslipidaemia involves a combination of these abnormalities.
3
Q
What is the role of LDL cholesterol in cardiovascular disease?
A
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.
4
Q
Why is HDL cholesterol referred to as “good” cholesterol?
A
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.
5
Q
What is the role of triglycerides in cardiovascular disease?
A
Elevated triglyceride levels can increase the size of lipid particles, contributing to plaque formation in arteries, which raises the risk of cardiovascular events.
6
Q
What are the primary risk factors for dyslipidaemia and cardiovascular disease?
A
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).
7
Q
How is dietary fat absorbed in the body?
A
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).
Flashcard
8
Q
How are lipids transported from enterocytes to the bloodstream?
A
Inside enterocytes, lipids are re-esterified into triglycerides and packaged with apolipoproteins into chylomicrons. These chylomicrons enter the lymphatic system, then the bloodstream.
9
Q
How are lipids carried in the blood?
A
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.
10
Q
What is the structure of bile salts (acids)?
A
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.
11
Q
What is the role of micelles in fat absorption?
A
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.
12
Q
What happens to bile salts after fat absorption?
A
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.
13
Q
What is the role of glycerol in fat digestion?
A
Glycerol is a product of triglyceride breakdown and is absorbed into enterocytes where it can be re-esterified into triglycerides or used for energy.
14
Q
How are bile salts recycled in the body?
A
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.
15
Q
What happens to the remaining 5% of bile salts?
A
About 5% of bile salts are eliminated in faeces. The liver compensates for this loss by synthesising more bile salts from cholesterol.
16
Q
Why might bile salts be a drug target?
A
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.
17
Q
How do bile salts aid in the absorption of dietary lipids?
A
Bile salts solubilise dietary lipids into micelles, allowing the lipids to pass through the diffusion barrier of the enterocytes for absorption.
18
Q
What role does Niemann-Pick C1-like 1 (NPC1L1) protein play in lipid absorption?
A
NPC1L1 facilitates the uptake of cholesterol across the brush border membrane of enterocytes during lipid absorption.
19
Q
Why might NPC1L1 be a drug target?
A
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.
20
Q
Where are chylomicrons formed and what is their primary function?
A
Chylomicrons are formed in enterocytes and are responsible for the uptake and transport of dietary lipids.
The main apolipoprotein component is ApoB48
21
Q
What is the composition of chylomicrons?
A
Chylomicrons contain 85–92% triglycerides, 6–12% phospholipids, 1–3% cholesterol, and 1–2% proteins.
22
Q
What happens to chylomicrons after they transport dietary lipids?
A
Chylomicron remnants are cleared by the liver after they have completed their lipid transport function.
23
Q
What are apolipoproteins and what role do they play in lipid transport?
A
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.
24
Q
In addition to being structural, what are some functions of apolipoproteins?
A
Apolipoproteins also act as ligands for lipoprotein receptors and activators/inhibitors of enzymes involved in the metabolism of lipoproteins.
25
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.
26
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.
27
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.
28
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.
29
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.
Flashcard
30
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.
31
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.
32
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.
33
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.
34
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.
35
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.
36
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.
37
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.
38
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.
39
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.
40
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.
41
What is the effect of loss-of-function mutations in LDLR (LDL receptor)?
Loss-of-function mutations in LDLR result in a reduced or absent activity of the LDL receptor, impairing the clearance of LDL cholesterol (LDL-C) from the bloodstream. This leads to elevated LDL-C levels, increasing the risk of atherosclerosis and cardiovascular disease.
42
What is the role of Apolipoprotein B (ApoB) in lipid metabolism?
Apolipoprotein B (ApoB) is a structural protein that forms the main protein component of lipoproteins like VLDL and LDL. It is essential for the binding of LDL to its receptor (LDLR) for the clearance of LDL from the blood. Loss-of-function mutations in ApoB can also lead to impaired LDL receptor binding and elevated cholesterol levels.
43
What is the impact of loss-of-function mutations in ApoB on cholesterol metabolism?
Loss-of-function mutations in ApoB result in reduced binding efficiency of LDL particles to LDL receptors, which impairs LDL-C clearance from the bloodstream, leading to elevated plasma LDL-C levels and an increased risk of atherosclerotic cardiovascular disease.
44
What is the function of HDL (High-Density Lipoprotein) in lipid metabolism?
HDL plays a crucial role in reverse cholesterol transport, where it transports cholesterol from peripheral tissues (like arteries) back to the liver for excretion or recycling, helping to reduce atherosclerotic risk. It is considered anti-atherogenic because it reduces cholesterol deposition in arterial walls.
45
How is HDL structured?
HDL has a cholesterol ester core (more hydrophobic), a high protein-to-lipid ratio, and a half-life of about 5 days. This structure aids in its function of transporting cholesterol and performing reverse cholesterol transport.
46
Where is HDL produced and removed from the body?
HDL is produced and removed by the liver. It helps to clear excess cholesterol from the bloodstream and tissues.
47
What role does Apo A-1 play in reverse cholesterol transport?
Apo A-1 mediates the interaction between HDL and the ATP-binding cassette transporter A1 (ABCA1), facilitating the transport of cholesterol out of lipid-laden macrophages, thus contributing to reverse cholesterol transport.
48
What are the key components of HDL in the context of cholesterol transport?
HDL contains free cholesterol (FC) and cholesteryl ester (CE). It transports free cholesterol from peripheral tissues, like macrophages, to the liver via reverse cholesterol transport.
49
What is the role of ABCA1 in reverse cholesterol transport?
ABCA1 (ATP-binding cassette transporter A1) facilitates the transfer of free cholesterol (FC) from lipid-laden cells (e.g., macrophages) to HDL, initiating reverse cholesterol transport.
50
What is reverse cholesterol transport, and how does HDL play a role in it?
Reverse cholesterol transport is the process by which HDL mediates the delivery of cholesterol (HDL-C) from peripheral tissues to the liver for excretion in bile. This process involves Apo A-1 interaction with SR-B1 (Scavenger Receptor B1).
Flashcard
51
How does SR-B1 contribute to HDL-C metabolism?
SR-B1 facilitates the uptake of HDL-C and cholesteryl ester (CE) into the liver, where the cholesterol can be excreted in bile. Additionally, SR-B1 can mediate HDL-C uptake by steroidogenic tissues for steroid hormone synthesis or cholesterol storage.
52
What is the function of SR-B1 in steroidogenic tissues?
In steroidogenic tissues, SR-B1 mediates the uptake of HDL-C for steroid hormone synthesis or cholesterol storage.
53
When does lipid accumulation (fatty streaks) begin, and when do clinical manifestations of lipid-related lesions become evident?
Lipid accumulation, or fatty streaks, begins in early childhood, but clinical manifestations of lipid-related lesions typically become evident in middle-aged adults, with a long latency period before they are clinically significant.
54
What are the components of the vascular wall as shown in a schematic?
The components of the vascular wall include:
PVAT: Perivascular adipose tissue
VSMC: Vascular smooth muscle cells
EC: Endothelial cells
EEL: External elastic lamina
IEL: Internal elastic lamina
BM: Basement membrane
55
How does the endothelial atherogenic phenotype contribute to atherosclerosis?
The endothelial atherogenic phenotype increases permeability to LDL, allowing more LDL-C to enter the vessel wall, which promotes atherosclerosis.
56
What are the key differences between "healthy" and "injured" endothelial cells?
Healthy Endothelium: Produces NO (Nitric Oxide) and PGI2 (Prostacyclin), which maintain vascular health and inhibit platelet aggregation.
Injured Endothelium: Loss of NO and PGI2 production, increased permeability, and increased production of ET-1 (Endothelin-1) and AngII (Angiotensin II), which promote vasoconstriction, inflammation, and atherogenesis.
57
What is the role of ET-1 and AngII in endothelial injury?
ET-1 and AngII contribute to endothelial dysfunction by promoting vasoconstriction, inflammation, and increased oxidative stress, further accelerating atherogenesis.
58
What happens when LDL oxidizes to oxLDL?
LDL oxidises to oxLDL (oxidized LDL), which is more atherogenic and contributes to oxidative stress and inflammation in the vessel walls.
59
What role do Reactive Oxygen Species (ROS) play in atherosclerosis?
ROS (Reactive Oxygen Species) are produced during oxidative stress and play a key role in the oxidation of LDL to oxLDL, which exacerbates endothelial injury, inflammation, and atherogenesis.
60
What is the relationship between oxLDL and inflammation?
oxLDL induces inflammation by activating inflammatory pathways in endothelial cells and immune cells, contributing to the development of atherosclerotic plaques.
61
What do activated endothelial cells release during atherosclerosis?
Activated endothelial cells release proinflammatory factors, including MCP-1 (monocyte chemotactic protein-1), and other adhesion molecules that recruit immune cells to the site of injury.
62
What is the role of MCP-1 in atherosclerosis?
MCP-1 attracts monocytes to the endothelial injury site, where they differentiate into macrophages, contributing to the formation of atherosclerotic plaques.
63
What is the role of MCP-1 (monocyte chemotactic protein-1) in atherosclerosis?
MCP-1 is a proinflammatory factor released by activated endothelial cells. It attracts monocytes to the site of endothelial injury, where they differentiate into macrophages, contributing to plaque formation in atherosclerosis.
64
How do monocytes mature into macrophages during atherosclerosis?
Monocytes attracted to the site of endothelial injury by proinflammatory factors like MCP-1 differentiate into macrophages. These macrophages engulf oxidised LDL (oxLDL) particles, contributing to the formation of foam cells and the development of atherosclerotic plaques.
65
How do monocytes mature into macrophages during atherosclerosis?
Monocytes attracted to the site of endothelial injury by proinflammatory factors like MCP-1 differentiate into macrophages. These macrophages engulf oxidised LDL (oxLDL) particles, contributing to the formation of foam cells and the development of atherosclerotic plaques
66
How do monocytes mature into macrophages during atherosclerosis?
Monocytes attracted to the site of endothelial injury by proinflammatory factors like MCP-1 differentiate into macrophages. These macrophages engulf oxidised LDL (oxLDL) particles, contributing to the formation of foam cells and the development of atherosclerotic plaques.
67
How do inflammatory mediators exacerbate atherosclerosis?
Inflammatory mediators such as cytokines and growth factors amplify the inflammatory signalling in atherosclerosis. These mediators increase oxidative stress, further damaging the endothelial cells, promoting monocyte recruitment, foam cell formation, and plaque progression. This creates a positive feedback loop, worsening the disease and contributing to plaque instability.
68
How does an atheroma plaque form, and what are its key components?
An atheroma plaque forms when foam cells accumulate in the vessel wall, along with other immune cells and extracellular matrix. The plaque contains a necrotic lipid core, composed of dead cells, cholesterol, and oxidised LDL. Over time, calcium salts may deposit in the plaque, increasing its stiffness and making the vessel more prone to rupture. This leads to atherosclerosis and increases the risk of cardiovascular events.
69
What are some key growth factors involved in the formation and progression of atherosclerotic plaques?
Key growth factors involved in atherosclerotic plaque formation and progression include:
Transforming growth factor-β (TGF-β): Stimulates the migration of smooth muscle cells and extracellular matrix production, contributing to plaque stability.
Heparin-Binding Epidermal Growth Factor-like Growth Factor (HB-EGF): Promotes smooth muscle cell proliferation and migration.
Platelet-derived growth factor (PDGF): Stimulates smooth muscle cell recruitment and proliferation, increasing plaque size.
Fibroblast growth factors (FGF): Involved in endothelial cell proliferation and the formation of new blood vessels (angiogenesis), which can support plaque development.
70
What is a stable plaque, and how does it differ from plaque progression in atherosclerosis?
Stable plaque: Characterised by a thick fibrous cap and a smaller lipid core, reducing the likelihood of rupture. It typically causes gradual narrowing of the artery without causing acute events.
Plaque progression: Refers to the continuous growth of atherosclerotic plaques, often involving an increase in lipid accumulation, smooth muscle cell proliferation, and extracellular matrix deposition, which can lead to plaque instability, increased risk of rupture, and the potential for acute cardiovascular events (e.g., heart attack or stroke).
71
What role do matrix metalloproteinases (MMPs) play in the formation of a vulnerable plaque in atherosclerosis?
Matrix metalloproteinases (MMPs) are enzymes that degrade components of the extracellular matrix, including collagen and elastin.
In vulnerable plaques, MMPs contribute to the thinning of the fibrous cap, weakening the plaque's structural integrity.
This can make the plaque more prone to rupture, leading to the formation of a thrombus (clot) and increasing the risk of acute cardiovascular events, such as heart attack or stroke.
72
What are the clinical manifestations of atherosclerosis?
Coronary Artery Disease (CAD): Chest pain (angina), heart attack (myocardial infarction), heart failure.
Cerebrovascular Disease: Stroke, transient ischemic attack (TIA).
Peripheral Arterial Disease (PAD): Leg pain (claudication), ulcers, gangrene.
Aortic Atherosclerosis: Abdominal or thoracic aortic aneurysm.
Renal Artery Stenosis: Hypertension, kidney failure.
Symptoms typically occur when a plaque disrupts blood flow, often resulting in sudden events like heart attacks or strokes.
73
What lifestyle factors decrease HDL levels?
Smoking (including passive smoking).
Obesity.
Excess caloric intake.
Sedentary behaviour.
Trans fatty acids, found in chips, cookies, cakes, and many fried fast foods.
74
What are cis fatty acids?
Cis fatty acids are unsaturated fatty acids where the hydrogen atoms are on the same side of the double bond, causing a bend in the chain. They are commonly found in natural fats and oils.
75
What are trans fatty acids?
Trans fatty acids are unsaturated fatty acids where the hydrogen atoms are on opposite sides of the double bond, resulting in a straighter chain. These are often formed during industrial processes, such as hydrogenation.
76
What are saturated fatty acids?
Saturated fatty acids have no double bonds between the carbon atoms and are saturated with hydrogen atoms. They are typically solid at room temperature and found in animal fats and some plant oils.
77
What are unsaturated fatty acids?
Unsaturated fatty acids have one or more double bonds between the carbon atoms. They are typically liquid at room temperature and found in plant oils, nuts, and fish.
78
What are monounsaturated fatty acids (MUFA)?
Monounsaturated fatty acids (MUFA) have one double bond in their fatty acid chain. Oleic acid, a common MUFA, is found in olive oil and has been linked to cardiovascular health benefits.
79
What are polyunsaturated fatty acids (PUFA)?
Polyunsaturated fatty acids (PUFA) contain more than one double bond in their carbon chain. They are found in fatty fish, flaxseeds, and walnuts, and are important for reducing inflammation and improving heart health.
80
What are polyphenols?
Polyphenols are plant compounds with antioxidant properties that help protect cells from oxidative stress. They are found in foods like fruits, vegetables, tea, and red wine, and have anti-inflammatory effects.
81
What are tocopherols?
Tocopherols are a group of compounds that make up vitamin E, a fat-soluble antioxidant. They help protect cells from oxidative damage and are found in vegetable oils, nuts, and seeds.
82
What is oleocanthal?
Oleocanthal is a polyphenolic compound found in extra virgin olive oil with anti-inflammatory and antioxidant properties. It has been shown to have similar effects to ibuprofen in reducing inflammation.
83
What are phytosterols?
Phytosterols (plant sterols) are plant-derived compounds that have a chemical structure similar to cholesterol. They are found in plant-based foods like vegetables, nuts, seeds, and oils.
84
How do phytosterols help reduce cholesterol levels?
Phytosterols block cholesterol absorption sites in the human intestine, which reduces cholesterol absorption, leading to lower blood cholesterol levels.
85
What is the effect of phytosterols on cholesterol absorption?
Phytosterols compete with cholesterol for absorption in the intestine, reducing the amount of cholesterol absorbed into the bloodstream, thus lowering serum cholesterol levels.
86
What is the role of micelles and lipoproteins in lipid absorption and distribution?
Micelles help absorb dietary lipids in the intestine, while lipoproteins (such as LDL and HDL) transport cholesterol in the bloodstream, with LDL-C delivering cholesterol to tissues and HDL-C transporting it back to the liver for excretion.
87
How does cholesterol affect health, and what is its origin?
Cholesterol is essential for cell membrane structure, hormone synthesis, and bile production. It is primarily endogenous (liver-derived), but plasma levels are also influenced by dietary intake.
88
What is the difference between LDL-C (Apo B-100) and HDL-C (Apo A-1)?
LDL-C (low-density lipoprotein) is considered "bad" cholesterol as it can deposit cholesterol in the artery walls, leading to atherosclerosis. HDL-C (high-density lipoprotein) is "good" cholesterol because it removes cholesterol from the arteries and transports it to the liver.
89
What is familial hypercholesterolaemia (FH) and how does it relate to cholesterol levels?
FH is a genetic condition that causes high cholesterol levels, typically due to mutations in the LDL receptor or Apo B-100, leading to excessive LDL-C in the blood and an increased risk of atherosclerosis.
90
What are the key steps involved in the development of atherosclerosis?
Atherosclerosis begins with endothelial injury, allowing LDL-C to penetrate the vessel wall, where it oxidises to ox-LDL. This leads to a fatty streak, inflammation, changes in vascular smooth muscle cell (VSMC) phenotype, and the formation of atherosclerotic plaques, which can be stable or unstable.
91
What are the major consequences of plaque rupture in atherosclerosis?
Plaque rupture can lead to the formation of a thrombus (blood clot), which can obstruct blood flow, resulting in heart attacks, strokes, or other cardiovascular events.
92
ow do dietary and lifestyle factors affect lipid levels and cardiovascular disease (CVD)?
Dietary choices (such as intake of fats, cholesterol, and fiber) and lifestyle factors (like physical activity, smoking, and alcohol consumption) can significantly influence lipid levels and the progression of CVD by affecting the balance between LDL-C and HDL-C levels.
93
What are the key processes involved in lipid transport from diet to blood?
Dietary Lipid Absorption:
Dietary fats (triglycerides) are emulsified by bile salts to form micelles.
Micelles allow lipids to cross the enterocyte membrane in the small intestine.
Inside enterocytes, chylomicrons are formed to transport lipids into the lymphatic system and eventually to the bloodstream.
Chylomicron Transport:
Chylomicrons carry dietary lipids (mainly triglycerides) through the bloodstream to peripheral tissues and the liver.
94
How is cholesterol transported in the circulation and what roles do lipoproteins/apolipoproteins play?
Lipoproteins:
LDL (Low-Density Lipoprotein): Carries cholesterol from the liver to peripheral tissues. Known as "bad cholesterol" due to its role in plaque formation in arteries.
HDL (High-Density Lipoprotein): Carries cholesterol from peripheral tissues back to the liver for excretion. Known as "good cholesterol" because it helps remove excess cholesterol from blood vessels.
Apolipoproteins:
ApoB-100: Found in LDL, important for LDL’s binding to LDL receptors for tissue uptake.
ApoA-1: Found in HDL, facilitates cholesterol efflux from cells to HDL.
95
What is meant by "good" and "bad" cholesterol?
Bad Cholesterol (LDL-C):
Transports cholesterol to tissues, including arterial walls. High levels of LDL-C increase the risk of atherosclerosis and cardiovascular disease (CVD).
Good Cholesterol (HDL-C):
Transports excess cholesterol from tissues back to the liver for excretion or recycling, thus protecting against atherosclerosis and CVD.
96
What is the basis of familial hypercholesterolaemia (FH) and its link to cardiovascular disease (CVD)?
Familial Hypercholesterolaemia (FH) is a genetic disorder caused by mutations in the LDL receptor or ApoB-100 gene, leading to reduced clearance of LDL cholesterol from the bloodstream.
As a result, there is a buildup of LDL-C in the blood, increasing the risk of atherosclerosis and premature CVD (e.g., heart attacks, strokes).
97
What is meant by reverse cholesterol transport?
A:
Reverse cholesterol transport refers to the process by which HDL removes excess cholesterol from peripheral tissues (like arterial walls) and transports it to the liver for excretion or recycling.
This process helps reduce cholesterol accumulation in the arteries and prevents atherosclerosis.
98
Outline the processes involved in the origins and development of atherosclerosis.
Endothelial Injury:
Injury or dysfunction of the endothelial cells (due to factors like smoking, high blood pressure, or high cholesterol) increases permeability to LDL-C.
Oxidation of LDL-C:
LDL-C oxidises into oxLDL, which triggers inflammation.
Inflammation and Foam Cell Formation:
Macrophages ingest oxLDL, forming foam cells that accumulate in the arterial walls.
Fatty Streak Formation:
Foam cells and lipids form fatty streaks in the arterial walls.
Plaque Formation:
Over time, the fatty streaks evolve into atherosclerotic plaques, which can be stable or unstable. Unstable plaques may rupture, leading to thrombosis and cardiovascular events.
99
Outline lifestyle variations that can affect lipid/cholesterol levels and cardiovascular disease (CVD).
Dietary Factors:
Saturated fats, trans fats, and cholesterol increase LDL-C levels.
Mono- and polyunsaturated fats (e.g., olive oil) and omega-3 fatty acids help raise HDL-C and lower LDL-C.
Phytosterols can block cholesterol absorption and help reduce LDL-C.
Exercise:
Regular physical activity can raise HDL-C and lower LDL-C and triglycerides, reducing the risk of CVD.
Smoking:
Smoking lowers HDL-C and increases LDL-C, promoting atherosclerosis and CVD.
Alcohol Consumption:
Moderate alcohol intake can increase HDL-C, but excessive drinking raises triglyceride levels and contributes to other health problems.
Body Weight:
Obesity increases LDL-C and triglycerides, and reduces HDL-C, raising CVD risk. Weight loss can help reverse these effects.
100
