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- ACE, angiotensin converting enzyme
- ACS, acute coronary syndrome
- CRP, C reactive protein
- Gp, glycoprotein
- HDL, high density lipoprotein
- IVUS, intravascular ultrasound
- LDD, local drug delivery
- LDL, low density lipoprotein
- LMWH, low molecular weight heparin
- MACE, major adverse cardiac events
- M-CSF, macrophage colony stimulating factor
- MMP, matrix degrading metalloproteinases
- PCI, percutaneous coronary intervention
- TMMP, tissue inhibitor of MMP
- UFH, unfractionated heparin
Clinical manifestations of coronary atherosclerosis are mainly a consequence of one of the following pathogenesis:
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Stable coronary artery plaque without thrombus formation causing variable degrees of luminal narrowing and stable angina
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Superficial plaque erosion, defined as endothelial erosions that may result in thrombus formation and acute coronary syndromes (ACS) (cause ∼30–40% of ACS, more common in younger patients and women)1
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Deep plaque rupture defined as fibrous cap rupture with exposed lipid core resulting in in-situ thrombus formation and varying degrees of coronary ischaemia (cause ∼60–70% of ACS).2
The lack of a linear relation between stenosis severity and the probability of developing an ACS is well recognised.3 Indeed the majority of plaques (∼70%) leading to acute myocardial infarction are not of angiographic significance, implying that factors other than stenosis severity determine the probability of vessel closure. The term “vulnerable” plaque defines the vascular substrate most subject to superficial erosion or plaque rupture which may in turn lead to ACS. While there are multiple complex risk and “trigger” factors at work, accurate identification of a “vulnerable” plaque and efficacious treatment to “stabilise” it, thereby reducing the risk of thrombotic induced acute events, would be of major clinical use. In this review we examine stabilisation and passivation of the “vulnerable” plaque by systemic and local drug delivery (LDD).
Plaque stabilisation can be defined by any intervention or interaction which, by causing a change in either the structure, content or function of an atherosclerotic plaque and/or the overlying endothelium, will either prevent or reduce the severity of erosion or rupture. Plaque passivation is defined as any intervention that decreases the thrombogenicity of the endoluminal oriented vascular surface.
Established risk factors of plaque vulnerability include:
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increased lipid content (> 40%)
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reduced collagen content in a thinned fibrous cap
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increased inflammatory cell infiltration, …