title: Small entities with large impact: microcalcifications and atherosclerotic plaque vulnerability.
abstract: OBJECTIVE
  Atherosclerotic plaque rupture and subsequent acute events, such as myocardial infarction and stroke, contribute to the majority of cardiovascular-related deaths. Calcification has emerged as a significant predictor of cardiovascular morbidity and mortality, challenging previously held notions that calcifications stabilize atherosclerotic plaques. In this review, we address this discrepancy through recent findings that not all calcifications are equivalent in determining plaque stability.
  
  
  RESULTS
  The risk associated with calcification is inversely associated with calcification density. As opposed to large calcifications that potentially stabilize the plaque, biomechanical modeling indicates that small microcalcifications within the plaque fibrous cap can lead to sufficient stress accumulation to cause plaque rupture. Microcalcifications appear to derive from matrix vesicles enriched in calcium-binding proteins that are released by cells within the plaque. Clinical detection of microcalcifications has been hampered by the lack of imaging resolution required for in-vivo visualization; however, recent studies have demonstrated promising new techniques to predict the presence of microcalcifications.
  
  
  CONCLUSIONS
  Microcalcifications play a major role in destabilizing atherosclerotic plaques. The identification of critical characteristics that lead to instability along with new imaging modalities to detect their presence in vivo may allow early identification and prevention of acute cardiovascular events.
authors.affiliation: Cardiovascular Medicine, Center for Interdisciplinary Cardiovascular Sciences and Center for Excellence in Vascular Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Hutcheson
authors.forename: Natalia
authors.initials: N
authors.lastname: Maldonado
authors.forename: Elena
authors.initials: E
authors.lastname: Aikawa
mesh_terms: D002114:Calcinosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D058226:Plaque, Atherosclerotic / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D020521:Stroke / Q000209:etiology / Q000378:metabolism / Q000473:pathology*