The Pathophysiology Of Atherosclerosis Flashcards
Atherosclerosis does not occur at random. Lesions occur at specific vessel sites such as
Bifurcations, Branch Points, and Regions of high curvature
Mechanical arterial endothelial injury causes
Atherogenic arterial blood flow patterns
Characterized by low flow, gradients, and flow reversal
Atherogenic
Cigarette smoking and diabetes both cause
Dyslipidemia
Dyslipidemia from cigarette smoking is caused by
Nicotine and oxidizing chemicals
The glycation of EC proteins and lipoproteins seen in diabetes causes
Diabetes
Evidence of lipoprotein deposition appears as early as age
20
Endothelial dysfunction allows entry and modification of lipids in the
Subendothelial space
Function in the absorption of dietary lipids
Lipoproteins
Transport triglycerides, cholesterol, and fat-soluble vitamins from the liver to peripheral tissues
Lipoproteins
Chylomicrons are formed with the truncated protein
ApoB-48
In the blood, what three proteins do chylomicrons acquire from HDL?
ApoA, ApoE, and ApoC
Primarily a triglyceride particle that transports dietary triglyceride to adipose tissue and muscle
Chylomicrons
What is the lipoprotein content of chylomicrons?
ApoC-II and ApoE (from HDL) and ApoB-48
Activated by ApoC-II on the CM surface
-Removes 80-90% of TAG in the muscle and adipose tissue
Lipoprotein Lipase
Chylomicrons remnants have ApoE-mediated uptake by
Hepatocytes
In the hepatic pathway, triglycerides (60%) and cholesterol (25%) are released as
VLDL
VLDL are released with which protein?
ApoB-100
ApoE and C as well as cholesterol esters are acquired from
HDL
Interacts with LPL to hydrolysis TGs to FFA in the periphery
VLDL
50% of VLDL remnants (aka IDLs) are cleared by hepatic receptors that recognize
ApoE
The remaining VLDL remnants are processed by hepatic triglyceride lipase and LPL to form
LDL
Most cholesterol in the blood is associated with
LDL
The normal role of LDL is to deliver cholesterol to the tissues for
Biosynthesis
What percentage of LDL are picked up by hepatocytes
-Remainder is by peripheral tissue
80%
LDL contain one apoprotein
ApoB-100
Has a high proposition of free cholesterol and cholesterol esters
LDL
LDL is recognized by the LDL receptor. This recognition process requires
ApoB-100
Involved in reverse cholesterol transport
HDL
Inherited disorders associated with severe elevations in total and LDL cholesterol result in
Accelerated Atherosclerosis
Autosomal dominant disorder characterized by severe elevations in total cholesterol and LDL-C
Familial Hypercholesterolemia
Homozygous familial hypercholesterolemia results in
Severely elevated cholesterol levels
Total cholesterol in homozygous Familial Hypercholesterolemia (FH) and LDLc levels are
Greater than 600 mg/dL
What are the LDLc levels in heterozygous FH?
Greater than 250 mg/dL
93% of cases of FH are due to mutations in the
LDL receptor
5% of FH cases are due to mutations in
-Inhibits binding of LDL to LDL-R
ApoB-100
2% of FH cases are due to a gain of function mutation in
-Enhances LDL-R degredation
PCSK9
Characterized by very high serum triglycerides
-Cholesterol is usually normal
Hyperlipoproteinemia (Type 1a)
Type 1a hyperlipoproteinemia is due to a deficiency in
Lipoprotein lipase OR ApoC-II
A clinical manifestation of type 1a hyperlipoproteinemia is
Eruptive Xanthomas
Proliferation and ECM synthesis helps to stabilize plaques with a
Fibrous Cover
Persistent inflammation leads to plaque disruption and
Vessel Thrombosis
Contribute to plaque progression and instability
Matrix Metalloproteinases
What are 4 modifiable risk factors of atherosclerosis?
Dyslipidemia, hypertension, cigarette smoking, and diabetes mellitus
Deals with delaying or preventing the onset of atherosclerosis
-Patients have no evidence of vascular disease
Primary prevention of atherosclerosis
May be. Marker for inflammation associated with atherogenesis
C reactive protein
Ancient, highly conserved protein that is an acute phase reactant
C-reactive protein
Released from the liver in response to inflammatory signals (i.e. IL-6)
C-reactive protein
A marker of inflammation associated with CAD
C-reactive protein
Similar to LDL and structurally related to plasminogen
Lipoprotein (a)
Is a 1.5-2x risk factor for CAD
Lipoprotein (a)
Independent risk factor for cardiovascular disease
Homocysteine
