title: Post-infarct cardiac rupture: recent insights on pathogenesis and therapeutic interventions.
abstract: Ventricular wall rupture represents a catastrophic complication of myocardial infarction (MI) in the clinic while research has long been hampered due to absence of suitable animal models. Since late 1990s, the mouse has become a suitable model for human post-infarct cardiac rupture. Here we review the clinical features of post-infarct rupture, factors associated with a higher risk of rupture, and findings from clinical trials on the incidence of post-infarct rupture. The features of the mouse model of post-infarct cardiac rupture are discussed. Research using this model suggests acute ventricular remodeling as the fundamental change leading to rupture, and has defined several key factors that determine the risk of rupture. We then provide a comprehensive review of the progress of experimental research in this field focusing on recent findings from genetically modified mouse models and experimental therapeutic interventions that reveal molecular mechanisms of post-infarct rupture. Genetic and pharmacological interventions targeting key inflammatory mediators, regulatory factors of extracellular matrix collagen and healing process effectively reduced the risk of rupture. These findings convincingly demonstrate that cardiac inflammation, damage to extracellular matrix proteins or blunted fibrotic healing constitute the central mechanisms for the pathogenesis of cardiac rupture and acute ventricular remodeling. Studies using the mouse model have also identified novel molecular mechanisms and therapeutic targets as well as suitable interventional regimens providing useful clues for clinical translation.
authors.affiliation: Experimental Cardiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Gao
authors.forename: David A
authors.initials: DA
authors.lastname: White
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Dart
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Du
mesh_terms: D000818:Animals; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006342:Heart Rupture, Post-Infarction / Q000188:drug therapy* / Q000209:etiology*; D006801:Humans; D009203:Myocardial Infarction / Q000150:complications*; D012307:Risk Factors; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology*