Signals Inking Ndothelial Damage, Platelet Adhesion And Smooth Muscle Migration And Proliferation In The Arterial Wall

Question 1

How did Russel Russ (when working on atherosclerosis) test Virchow’s hypothesis?

Answer 1

He induced a superficial mechanical damage to the endothelium of an artery (using a balloon catheter) and observed the response

Question 2

Following superficial mechanical endothelial damage, what occurs on the surface of the artery?

Answer 2

Within 30 minutes the injured area is covered by platelets.

They secrete PDGF, creating a local gradient which is a chemoattractant to smooth muscle cells

Question 3

What role did Russ suppose platelets which covered endothelial damage played?

Answer 3

He proposed that the platelets contain and release an agent which is a powerful mitogen for smooth muscle cells -> This agent is known as platelet derived growth factor (PDGF)

Question 4

What evidence did Russ have that PDGF existed?

Answer 4

• Serum sustains the growth of smooth muscle cells much better than plasma, and the difference between serum and plasma is the clot reaction

Question 5

Describe structure/forms of PDGF

Answer 5

PDGF has several isoforms, which pair together to form homodimers or heterodimers

Question 6

Where does PDGF recall smooth muscle cells from? What do they do next?

Answer 6

SM cells from the tunica media. PDGF then induced their proliferation in the intima, where they form the early stage lesion (focal intimal thickening)

Question 7

Once in the intima, describe the phenotype switch of the SM cells

Answer 7

They switch from a contractile phenotype to a ‘synthetic phenotype’. Unable to contract, responding well to mitogens, producing collagen and other ECM components - become more fibroblast-like

Question 8

The development of atherosclerosis is due to a __________ and an ___________ response

Answer 8

Proliferative; inflammatory