Atherosclerosis Flashcards
What are the 3 stages of plaque development?
1) Fatty streak- results from endothelial dysfunction, lipoprotein entry and modification, leukocyte recruitment, and foam cell formation.
2) Plaque progression- results from smooth cell migration, altered matrix syntehsis, and lipid core formation.
3) Plaque disruption: plaque’s integrity is disrupted and thrombus is formed.
What happens to the underlying material over of protective fibrous cap after decades of development?
Plaque aquires a thrombogenic lipid core
How is size and concentration of Lipoprotein (a) affected by diet or other factors?
It is not affected; size and concentration of Lipoprotein(a) is genetically determined.
What is a inflammatory marker associated with CAD? Why is this useful?
C-reactive protein, highly conserved protein that is an acute phase reactant- it is released from the liver in response to inflammatory signals. It could be used to detect early atherosclerosis or people at risk.
Definition of atherosclerosis
Endothelial cell damage/dysfunction of muscular and elastic arteries (large and small arteries), characterized by a fibrous cap and an atheromatous core within the tunica intima.
Functions of normal healthy endothelium (4)
1) Modification of vascular tone
2) Modulation of immune response (anti-inflammatory until injured)
3) Anti-hypertrophic properties
4) Anticoagulant/anti-thrombolytic/ pro-fibrinolytic functions
How does endothelium modulate vascular tone?
They secrete substances that modulate contraction of SMC in tunica media (e.g. vasodilators including NO and prostacyclin and vasoconstrictors including endothelin)
When do atherosclerotic plaques become clinically apparent and how does it present?
They present as stable/unstable angina when the plaques become obstructive, decreasing the diameter of the arterial lumen and blocking blood flow.
What happens when the fibrous cap of an atherosclerotic plaque ruptures?
It exposes prothrombotic molecules within the lipid core (e.g. tissue factors from foam cells) to the blood, activating coagulation and formation of a thrombus. This can result in occlusion of an arterial lumen, resulting in ischemia of tissue.
Which sites of arteries are most prone to lesions in atherosclerosis and why?
Most vulnerable locations: Bifurcations, branch points, and regions of high curvature.
Reason: At these locations, laminar blood flow is disrupted, as the flow becomes more turbulent/static (low blood flow near wall of vessel). This “atherogenic” arterial blood flow pattern disturbs shear, altering enodthelial cell phenotype and behavior.
Myocardial infarction, angina, stroke, Ischemic bowel disease, Abdominal aneurysm, and peripheral vascular disease are all complications of what
Atherosclerosis
In what ways does chemical endothelial cell injury affect behavior their (5)
1) Release of inflammatory cytokines
2) Increase cell surface adhesion molecules (leukocyte recruitment)
3) Altered release of vasoactive substances (decreased NO and prostacyclin secretion)
4) ROS production
5) Prothrombotic
Primary prevention vs. secondary prevention
Primary prevention: deals with delaying or preventing onset of athterosclerosis (pt has no evidence of vascular disease). Doctor decides whether putting them on prevention protocol is beneficial due to risk factors.
Secondary prevention: Relies on early detection of disease process. Pt already has disease and doctor decides what intervention to use to prevent progression of disease.
Steps of endogenous pathway of lipid metabolism
1) Liver packages cholesterol and trigylcerides into VDLD particles, accompanied by Apo B-100 and are released into circulation.
2) VLDL interacts with LPL receptors in endothelium, releasing FFA and Triglycerides into periphery (muscle/ adipose tissue), forming VLDL remnants called IDLs.
3) 50% of IDLs are cleared by hepatic receptors that recognize ApoE (acquired from circulation).
4) Remaining IDL is processed by LPL and hepatic triglyceride lipase, in which triglycerides, apo E, and apo C are removed, forming LDL particles. LDL particles only have B-100 apoproteins left.
5) LDL is cleared in plasma via LDL receptor mediated endocytosis in the liver and peripheral cells (via ApoB-100). Cholesterol can be used by these cells to be stored, or make membrane components like steroids.
What are the earliest visible lesions of atherosclerosis and what are their symptoms?
Fatty streaks; they appear as yelow discoloration of artery’s inner surface but they neither protrude substantially into arteiral lumen or impeded blood flow. They are asymptomatic.
What are examples of antithrombotic molecules produced by normal epithelium?
Heparan sulfate + thrombomodulin
Stable vs. unstable angina
Unstable angina is chest pain even at rest while stable angina is chest pain only during exertion.
How is homocysteine linked to atherosclerosis?
Homocysteine is an independent risk factor for CV disease. Researchers know homocystein levels are linked to atherosclerosis but lowering it doesn’t have an effect.
Inheritance pattern of familial hypercholesterolemia
Incompletely dominant. Homozygous pts have severely elevated cholesterol levels and TAG levels are WNL. Heterozygous have moderately elevated cholesterol levels.
Steps in development of atherosclerosis (5)
1) Endothelial dysfunction + injury
2) Lipoprotein entry and modification in subendothelial space
3) Inflammation
4) Leukocyte + SMC recruitment
5) SMC proliferation + ECM deposition
What are risk factors for chemical arterial endothelial injury?
Risk factors:
1) Dyslipidemia
2) Cigarette smoking (nicotine + oxidizing chemicals)
3) Diabetes (glycation of endothelial cell proteins and lipoproteins)
Modifiable risk factors of atherosclerosis (4)
1) Smoking
2) HTN
3) hyperlipidemia
4) DM
How does the structure of fibrous cap contribute to plaque integrity?
Although plaques with thick fibrous caps can narrow the arteries significantly, they are less likely to rupture. Plaques with thinner caps are less obstructive but are more likely to rupture.
