title: Altered melusin pathways involved in cardiac remodeling following acute myocardial infarction.
abstract: BACKGROUND
  Melusin, a muscle-specific integrin-linked protein, has been reported to be a biomechanical sensor and to protect the heart from pressure overload. In the present study, we investigated the possible role that melusin plays during cardiac remodeling after myocardial infarction (MI).
  
  
  METHODS
  We constructed a heart failure model of rats induced by left anterior descending coronary artery ligation. At different time points (1, 2, 3, 4, 6, and 8 weeks) following the operation, cardiac function was monitored by echocardiography and hemodynamic assessment; cardiac morphology was measured using hematoxylin-eosin-stained sections. Melusin expression, as well as p-Akt, Akt, and one of the Rho small GTPase family members, CDC42, was determined dynamically by Western blotting analysis during the postinfarction cardiac remodeling.
  
  
  RESULTS
  Progressive increase in left ventricular (LV) end-systolic dimension and LV end-diastolic dimension and decrease in percent LV fractional shortening (%FS) and LVdp/dt(max) demonstrated gradually deteriorated cardiac function in rats following MI operation. Morphological analysis revealed cardiac remodeling in MI animals, including increased LV diameter and decreased border zone thickness. We also showed a dynamic change in melusin during heart failure progression; it had an initial decline which was evident at 3 weeks and increased subsequently, reaching peak levels at 6 weeks. This dynamic change in melusin was significantly correlated with %FS and LVdp/dt(max.) p-Akt/Akt and CDC42 protein expression was correlated with melusin content.
  
  
  CONCLUSIONS
  The altered melusin pathways and CDC42 parallel the cardiac function progression during cardiac remodeling post-MI. The dynamic change of them during this procedure may represent an important molecular mechanism underlying postinfarction cardiac remodeling and provide potential therapeutic targets.
authors.affiliation: Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Gu
authors.forename: Di
authors.initials: D
authors.lastname: Zheng
authors.forename: Jian
authors.initials: J
authors.lastname: Bai
authors.forename: Jun
authors.initials: J
authors.lastname: Xie
authors.forename: Qing
authors.initials: Q
authors.lastname: Dai
authors.forename: Biao
authors.initials: B
authors.lastname: Xu
mesh_terms: D000818:Animals; D001835:Body Weight; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D004452:Echocardiography; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006439:Hemodynamics; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling / Q000502:physiology*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; C492400:ITGB1BP2 protein, human; D009124:Muscle Proteins; D020764:cdc42 GTP-Binding Protein