title: Intraplaque haemorrhages as the trigger of plaque vulnerability.
abstract: Atherothrombosis remains one of the main causes of morbidity and mortality in the western countries. Human atherothrombotic disease begins early in life in relation to circulating lipid retention in the inner vascular wall. Risk factors enhance the progression towards clinical expression: dyslipidaemia, diabetes, smoking, hypertension, ageing, etc. The evolution from the initial lipid retention in the arterial wall to clinical events is a continuum of increasingly complex biological processes. Current strategies to fight the consequences of atherothrombosis are orientated either towards the promotion of a healthy life style and preventive treatment of risk factors, or towards late interventional strategies. Despite this therapeutic arsenal, the incidence of clinical events remains dramatically high, dependent, at least in part, on the increasing frequency of type 2 diabetes and ageing. But some medical treatments, focusing only on prevention of the metabolic risk, have failed to reduce cardiovascular mortality, thus illustrating that our understanding of the pathophysiology of human atherothrombosis leading to clinical events remain incomplete. New paradigms are now emerging which may give rise to novel experimental strategies to improve therapeutic efficacy and prediction of disease progression. Recent studies strengthen the concept that the intraplaque neovascularization and bleeding (Figure 1, upper panel) are events that could play a major role in plaque progression and leucocyte infiltration, and may also serve as a measure of risk for the development of future events. The recent advances in our understanding of IntraPlaque Hemorrhage as a critical event in triggering acute clinical events have important implications for clinical research and possibly future clinical practice.
authors.affiliation: UMR 698 Inserm, Paris 7-Denis Diderot University, Xavier Bichat Hospital, 46 rue Henri Huchard, 75018 Paris, France. jean-baptiste.michel@inserm.fr
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
authors.forename: Renu
authors.initials: R
authors.lastname: Virmani
authors.forename: Eloïsa
authors.initials: E
authors.lastname: Arbustini
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D003952:Diagnostic Imaging; D017700:Embolism, Cholesterol / Q000209:etiology* / Q000517:prevention & control; D004912:Erythrocytes / Q000378:metabolism; D006454:Hemoglobins / Q000096:biosynthesis; D006470:Hemorrhage / Q000150:complications* / Q000276:immunology / Q000473:pathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007111:Immunity, Cellular; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D010447:Peptide Hydrolases / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D012307:Risk Factors
chemical_list: D020533:Angiogenesis Inhibitors; D015415:Biomarkers; D006454:Hemoglobins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010447:Peptide Hydrolases