Lecture 25 Flashcards
Where does cholesterol in the body come from?
Diet and is synthesized in the liver.
Cholesterol biosynthesis happens where in the body?
Liver
These are spherical structures with an outer wall made of phospholipids, cholesterol, and proteins (apolipoproteins) that carry cholesterol and triglycerides (TAG) within the body.
Lipoproteins
Transports dietary cholesterol and triglycerides to various tissues in body
Chylomicrons
Transports mostly triglycerides from liver to adipose tissue
VLDL (very low density lipoprotein)
Remnant of VLDL after it delivers triglycerides to tissue; May be cleared from the blood via direct uptake by the liver or remodeled into LDL
IDL (intermediate density lipoprotein) also called VLDL remnant
- Transports mostly cholesterol from liver to various tissues of body
- Removed from circulation via LDL receptors in the liver
LDL (low density lipoprotein)
i. Transports cholesterol from peripheral tissues back to liver where it can be excreted via bile
HDL (High density lipoprotein)
This type of lipoprotein is antiatherogenic
HDL (High density lipoprotein)
Has:
- antiinflammatory properties
- antioxidant properties
- inhibits LDL oxidation
- inhibits monocyte migration into subendothelial space
- Prothrombic properties
Antiatherogenic
Unhealthy blood cholesterol levels, high BP, smoking, insulin resistance, diabetes, hyperglycemia, obesity and physical inactivity are risk factors for what disease?
Atherosclerosis
This is the space between the basement membrane and the internal elastic lamina where fatty streaks develop
Subendothelial space
This type of injury allows LDL to infiltrate into subendothelial space of the artery
Endothelial artery
Oxidized LDL (oxLDL) in subendothelial space and altered expression (increase) of adhesion molecules on vessel wall due to endothelial injury cause this to happen.
Migration of monocytes and T-cells
When monocytes migrate into subendothelial space, they differentiate into _________ with scavenger receptors.
Macrophages
Macrophages endocytose ______ in the subendothelial space
oxLDL
Foam cell formation and formation of fatty streaks in subendothelial space are casued by what?
oxLDL endocytosis by macrophages
Release of _____ by foam cells and T cells in subendothelial space cause:
- smooth muscle migration and proliferation (rapid reproduction)
- formation of fibrous cap
- preceipitation of calcium
Cytokines
Once calcium preciptates into the subendothelial space, this is formed in the artery.
Hard plaque
Plaque rupture can lead to ___ formation
Clot
This is when a vessel ruptures due to the weakening of vessel wall leads to dilation or “ballooning”
Aneurysm
This is turbulent blood flow in regions o curvature or bifurcation which can cause endothelial damage
Shear stress
Smoking causes carbon monoxide injury to endothelium and _____ rate of LDL oxidation.
Increased
Causes of endothelial injury
Shear stress, hypertension, smoking
True or False? When LDL concentration is higher, the LDL molecule circulates longer before it is removed.
True
The longer the LDL circulates, the the fraction of LDL that will enter the wall and become oxidized increases or decreases?
Increases
This growth factor normally functions to protect vessels against injury
TGF-beta
Does LDL enhance or suppress the activity of TGF beta?
Suppress
- Increases vascular smooth muscle cell proliferation
- Increases macrophage engulfment of oxLDL
- Decreases endothelial nitric oxide production
- Increases the production of advanced glycation end-products (AGEs).
Role of hyperglycemia in atherosclerosis
An ___ is a result of a chain of chemical reactions after an initial non-enzymatic glycation (sugar attachment) of a protein or lipid; this changes the structure and function of proteins and lipids
AGE - advanced glycation end-product
-Promote cross-linking of proteins in arterial wall leading to trapping of oxLDL molecules
AGE
-Alters ECM (extracellular matrix) proteins leading to a decrease in vascular compliance
AGE
-Generate ROS (enhance neutrophil respiratory burst)
AGE
-Stimulate inflammatory and pro-thrombotic signaling in endothelial cells, macrophages, and vascular smooth muscle cells
AGE
Pharmacological therapy for atherosclerosis involving HMG CoA Reductase inhibitors
Statins
Pharmacological therapy for atherosclerosis that a. lowers LDL by blocking intestinal absorption of cholesterol
Cholesterol absorption inhibitors
Pharmacological therapy for atherosclerosis that decreases VLDL secretion by liver which lowers LDL and decreases catabolism of HDL leading to elevated levels of HDL
Niacin
Pharmacological therapy for atherosclerosis that increases clearance of triglyceride rich lipoproteins (VLDL, chylomicrons) and increases HDL
Fibric acid derivatives
Pharmacological therapy for atherosclerosis by lowering LDL by binding bile acids in GI tract leading to increased elimination in stool which forces liver to use cholesterol to synthesize more bile acids. Also, Increases LDL receptor expression in liver which enhances removal of LDL from circulation
Bile acid sequestrants
