1 of 40

Atherosclerosis

2 of 40

Which layer of the artery does atherosclerosis affect?

3 of 40

Atherosclerosis

  • Vascular intima
  • Atheromas or atheromatous plaques
  • Intimal thickening
  • Lipid accumulation
  • Narrowing/obstruction of the vessel lumen
  • Weaken the media

​

​

4 of 40

What is an atheroma?

5 of 40

Atheroma

  • Raised lesion that begins within intima
  • Soft, yellow, grumous lipid core
  • Fibrous cap

6 of 40

What does an atheroma consist of?

7 of 40

Atheroma

  • Cells: smooth muscle (migration of tunica media), macrophages (inflammation response), leukocytes
  • ECM: collagen, elastic fibers, proteoglycans
  • Lipids

​

8 of 40

What are the causes of endothelial injury?

9 of 40

Endothelial Injury

  • Hypercholesterolemia: raises ROS → impairs endothelial cell function
  • Hemodynamic: HTN → turbulent blood flow → stress
  • Cigarette smoke
  • Increased homocysteine
  • Viruses
  • Bacteria

10 of 40

What is the role of C-reactive protein?

11 of 40

CRP

  • Acute phase reactant from liver
  • Increases via inflammatory mediators
  • Augments immune response by activating complement cascade
  • Marker of risk for MI, stroke, PAD, and sudden cardiac death

12 of 40

What is the pathogenesis of atherosclerosis?

13 of 40

Pathogenesis

  • Endothelial damage → increased permeability
  • WBCs adhere + thrombosis
  • Accumulation of lipids in vessel wall
  • Oxidation of lipids → foam cells
  • Smooth muscles migrate from media to intima (via PDGF and FGF)
  • Smooth muscle cells proliferate and produce ECM → plaque matures

14 of 40

15 of 40

What is the role of inflammation in atherosclerosis?

16 of 40

Inflammation

  • Triggered by accumulation of cholesterol crystals and free fatty acids
  • Dysfunctional endothelial cells → VCAM-1 → binds monocytes and T lymphocytes
  • Monocytes travel to intima and engulf oxidized LDL
  • Macrophages produce IL-1, TNF, and chemokines → increased adhesion
  • Chronic inflammatory state

17 of 40

How does the plaque mature and stabilize?

18 of 40

Maturation/Stabilization

  • Smooth muscle cells migrate from media to intima
  • Growth factors such as PDGF, FGF, and TGF contribute to smooth muscle cell proliferation
  • Smooth muscle cells in vessel wall make ECM (esp. collagen) which stabilize plaques

​

​

19 of 40

20 of 40

What can after the formation of a plaque?

21 of 40

What can happen next?

  • Hemorrhage into plaque → extend plaque or induce rupture
  • Ulceration
  • Erosion → thrombosis → occlusion
  • Atheroembolism
  • Aneurysm formation leads to wall weakness

​

​

22 of 40

What is the difference between a vulnerable and a stable plaque?

23 of 40

Stable vs Vulnerable

Stable

  • Small lipid core
  • Few macrophages
  • Thick fibrous cap

Vulnerable

  • Many foam cells
  • A lot of lipid
  • Many inflammatory cells
  • Thin fibrous cap

​

Likely to rupture!!

24 of 40

25 of 40

How does inflammation contribute to a weak fibrous cap?

26 of 40

Vulnerable Plaques

  • Major structural component is collagen – establishes strength and determines plaque stability
  • Collagen made by smooth muscle cells and degraded by metalloproteinases (enzymes from macrophages in atheroma)

​

Inflammation destabilizes plaque integrity!!

​

27 of 40

What are some complications of atherosclerosis?

28 of 40

Complications

  • Coronary artery disease
  • Ischemia
  • Infarcts
  • Peripheral vascular disease
  • Thrombus
  • Emboli
  • Aneurysms

29 of 40

What are some defining features of coronary artery disease?

30 of 40

Coronary Artery Disease

  • Ischemic heart disease → most likely have atherosclerosis of one or more coronary arteries
  • Either progressive stenosis of lumen (chronic, “fixed” obstruction) or acute plaque disruption with thrombosis (sudden, dynamic)
  • 75 % stenosis – symptomatic ischemia induced by exercise
  • 90 % stenosis – inadequate coronary blood flow at rest

​

​

31 of 40

What is the difference between angina pectoris and myocardial infarction?

32 of 40

Ischemia

  • Myocardial ischemia – imbalance between supply and demand for oxygenated blood

​

  • Angina pectoris: less severe ischemia, no death of cardiac muscle
  • Myocardial infarction: death (necrosis) of cardiac muscle

​

33 of 40

What are the three types of angina?

34 of 40

Stable (typical) angina:

  • Reduced coronary perfusion secondary to stenosis
  • Usually not associated with plaque disruption
  • Relieved by rest or nitroglycerin (vasodilator)

Unstable angina:

  • Increased progressive frequency, usually at rest, more prolonged
  • Disruption of plaque with superimposed partial thrombosis or vasospasm (preinfarction angina)

Prinzmetal angina:

  • Occurs at rest due to coronary artery spasm
  • Unrelated to exercise, heart rate, or BP
  • Relieved by nitroglycerin or calcium channel blockers
  • ST elevation

​

​

35 of 40

How does an acute coronary syndrome happen?

36 of 40

Acute Coronary Syndrome

  • Unstable angina, acute MI, and sudden cardiac death
  • Usually precipitated by abrupt atherosclerotic plaque change/rupture followed by thrombosis

​

37 of 40

What is the role of vasoconstriction in acute coronary syndromes?

38 of 40

Vasoconstriction

  • Constricting lumen → narrowing size and promoting plaque disruption
  • Stimulated by factors such as circulating adrenergic agonist, locally released platelet contents, etc.

​

39 of 40

What are most acute coronary syndromes associated with?

40 of 40

Coronary Thrombosis

  • Most acute coronary syndromes associated with disruption of the AS plaque
  • MI often occurs when thrombus is superimposed on disrupted (previously partially stenotic) plaque → total occlusion
  • Many ruptured plaques with subsequent coronary thrombosis resulting in MI occur in coronary arteries which were previously only partially stenotic (many less than 70% stenosis)

​

​