Mechanism and prevention of restenosis Flashcards
What are the surgical interventions for acute coronary syndromes?
- Balloon angioplasty
* Stent
What is restenosis?
re-occlusion of vessel through scar tissue that forms around the site of stent
Rates of restenosis for:
- Balloon angioplasty
- Bare-metal stent (BMS)
- Drug eluting stent (DES)
- Balloon angioplasty: 50%
- Bare-metal stent (BMS): 20-30%
- Drug eluting stent (DES): 5-10%
Risk factors involved in the development of restenosis?
- Clinical (diabetes, history of restenosis)
- Biological (increased PAI-1)
- Genetic (NOS3 polymorphisms)
- Lesion-related risk factors (number and length of lesions, calcification, tortuous vessel)
- Procedural (balloon angioplasty, BMS)
How do the risks eventually lead to restenosis?
- The patient specific risk factors lead to inflammation
- Inflammation drives VSMC proliferation and migration into the lumen of vessel
- inflammatory response caused by risk factors can increase platelet activation
- extracellular matrix deposition and neointimal hyperplasia happens leading to restenosis
How can stents cause restenosis?
after stent gets introduced there’s opening of vessel but re-occlusion and narrowing can happen, scar tissue starts to infiltrate into lumen
How can smoking play a role in causing restenosis?
- Smoking can induce reactive oxidation species
- oxidised products induce neointima proliferation, proliferation of VSMC and extracellular matrix deposition
- Causes stiffening and thickening of vessels
How do matrix metalloproteinases lead to restenosis?
Matrix metalloproteinases can lead to ECM deposition
What are the steps of restenosis after a stent gets put in?
- Endothelial erosion and platelet/fibrinogen deposition right after the stent is put in
- Cytokine release and leukocyte recruitment
- Smooth muscle cell proliferation and migration, and leukocyte infiltration
- Macro recruitment of smooth muscle cells and they continue to proliferate - neointimal growth
- A restenotic lesion forms - flow of blood is reduced, vessel can become fully occluded
What are the triggers for restenosis?
EC denudation and EC dysfunction are the triggers for restenosis – trauma activates coagulation (cause fibrin formation)
What are some important mediators secreted post stent?
- Cytokines ie IL-6 and 8
- leukocyte recruitment
- monocyte chemo attractive protein – recruits more immune cells
- various different growth factors also released
What happens to the smooth muscle cell phenotype?
Smooth muscle cells switch to proliferative phenotype
What are the different types of metal coronary stents?
1st generation:
- Made of stainless steel
- Cypher and Taxus
2nd generation:
- Made of cobalt chromium
- Xience and Endeavor
3rd generation:
- Made of Platinum Chromium
- Promus
Stents got thinner with each generation – prevents restenosis
What do drug-eluting stents do?
Drug-eluting stents cause a significant reduction in restenosis rates as compared with bare-metal stents
What drugs are stents usually coated with?
- sirolimus
- paclitaxel
- everolimus
- zotarolimus