From intraplaque haemorrhages to plaque vulnerability

Abstract

Intraplaque hemorrhages are mainly related to inward neoangiogenesis, initiated from the adventitia by lipid-dependent outwardly convected signals, and by the immaturity of these neovessels, allowing leaks and hemorrhages. Repeated intraplaque hemorrhages play a major role in the evolution of thrombotic occlusive disease, similar to the role of intraluminal thrombus in the progression of abdominal aortic aneurysm toward rupture. Red blood cells (RBCs) are an important source of unesterified cholesterol, because their membranes are particularly cholesterol rich. This unesterified cholesterol is rapidly organized in cholesterol crystals, highly toxic for cell and membranes. Oxidized cholesterol and LDL provoke the irreversible covalent aggregation of proteins, including hemoglobin, forming ceroids, which are also highly toxic. Hemoglobin play a major role of prooxydant molecules in this context, by its ability to release heme and iron, the main catalyser of oxidative reaction. In the context of type 2 diabetes, the oxidative potential of intraplaque-free hemoglobin play a predominant role in the progression of atherothrombotic disease toward clinical expression. Associated to RBC, intraplaque hemorrhages convey leukocyte, mainly neutrophils in human, and plasma zymogen that are the main source of proteases, including coagulation proteases, activation of the fibrinolytique system, release of leukocyte serine proteases and cathepsins and activation of MMPs. These proteases concentrate in the hemorrhagic/necrotic core rendered plaque highly vulnerable. An adaptive immune response takes place in the adventitia, in regard of hemorrhagic plaques, in relation to outwardly convected oxidized or proteolyzed neoantigens, and chemokinic signals. Finally, intraplaque hemorrhages and thrombi are the site of weak pathogen entrapment, which promote all these oxydative and proteolytic phenomenons.

Plaque hemorrhage in carotid artery disease: Pathogenesis, clinical and biomechanical considerations

“…2) and plaque progression (Moreno et al, 2012). PH also carries proteolytic enzymes, causing thinning of the FC and making the plaque liable to rupture (Michel et al, 2012). Readers are directed to other excellent articles (Levy and Moreno, 2006; Michel et al, 2011) for further relevant pathological details, as they are beyond the scope of this review.…”

Predictors of Inappropriately Rapid Coronary Lesion Progression in Patients Undergoing Percutaneous Coronary Interventions

“…The notion that certain processes or medications can lead to IPH may change the way we approach certain patients; Michel et al. found that IPH enhances plaque vulnerability and independently can increase the tendency for plaque rupture, 24 and if these combined results are to be verified in a dedicated event-driven clinical trial, they may have an impact on the decision to initiate IIB3A inhibitors in the event of a thrombus-rich plaque during PCI.…”

Association of Age and Size of Carotid Artery Intraplaque Hemorrhage and Minor Fibrous Cap Disruption: A High Resolution Magnetic Resonance Imaging Study

“…In the initial phase of IPH, leukocytes, particularly neutrophils, and plasma zymogen were conveyed in plaque with the RBC entrance. These two components of fresh IPH were the key sources of proteases, such as coagulation proteases, leukocyte serine proteases, and gelatinase, which accounted for a major part of the proteolytic degradation of fibrous cap 15 ) . Neutrophil gelatinase and serine protease are mainly conveyed by bleeding within plaques, which are capable of degrading the extracellular matrix.…”