title: Biglycan is required for adaptive remodeling after myocardial infarction.
abstract: BACKGROUND
  After myocardial infarction (MI), extensive remodeling of extracellular matrix contributes to scar formation and preservation of hemodynamic function. On the other hand, adverse and excessive extracellular matrix remodeling leads to fibrosis and impaired function. The present study investigates the role of the small leucine-rich proteoglycan biglycan during cardiac extracellular matrix remodeling and cardiac hemodynamics after MI.
  
  
  RESULTS
  Experimental MI was induced in wild-type (WT) and bgn(-/0) mice by permanent ligation of the left anterior descending coronary artery. Biglycan expression was strongly increased at 3, 7, and 14 days after MI in WT mice. bgn(-/0) mice showed increased mortality rates after MI as a result of frequent left ventricular (LV) ruptures. Furthermore, tensile strength of the LV derived from bgn(-/0) mice 21 days after MI was reduced as measured ex vivo. Collagen matrix organization was severely impaired in bgn(-/0) mice, as shown by birefringence analysis of Sirius red staining and electron microscopy of collagen fibrils. At 21 days after MI, LV hemodynamic parameters were assessed by pressure-volume measurements in vivo to obtain LV end-diastolic pressure, end-diastolic volume, and end-systolic volume. bgn(-/0) mice were characterized by aggravated LV dilation evidenced by increased LV end-diastolic volume (bgn(-/0), 111+/-4.2 microL versus WT, 96+/-4.4 microL; P<0.05) and LV end-diastolic pressure (bgn(-/0), 24+/-2.7 versus WT, 18+/-1.8 mm Hg; P<0.05) and severely impaired LV function (EF, bgn(-/0), 12+/-2% versus WT, 21+/-4%; P<0.05) 21 days after MI.
  
  
  CONCLUSIONS
  Biglycan is required for stable collagen matrix formation of infarct scars and for preservation of cardiac hemodynamic function.
authors.affiliation: Abteilung für Kardiologie und Pneumologie, Charite-Universitätsklinikum Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Westermann
authors.forename: J
authors.initials: J
authors.lastname: Mersmann
authors.forename: A
authors.initials: A
authors.lastname: Melchior
authors.forename: T
authors.initials: T
authors.lastname: Freudenberger
authors.forename: C
authors.initials: C
authors.lastname: Petrik
authors.forename: L
authors.initials: L
authors.lastname: Schaefer
authors.forename: R
authors.initials: R
authors.lastname: Lüllmann-Rauch
authors.forename: O
authors.initials: O
authors.lastname: Lettau
authors.forename: C
authors.initials: C
authors.lastname: Jacoby
authors.forename: J
authors.initials: J
authors.lastname: Schrader
authors.forename: S-M
authors.initials: SM
authors.lastname: Brand-Herrmann
authors.forename: M F
authors.initials: MF
authors.lastname: Young
authors.forename: H P
authors.initials: HP
authors.lastname: Schultheiss
authors.forename: B
authors.initials: B
authors.lastname: Levkau
authors.forename: H A
authors.initials: HA
authors.lastname: Baba
authors.forename: T
authors.initials: T
authors.lastname: Unger
authors.forename: K
authors.initials: K
authors.lastname: Zacharowski
authors.forename: C
authors.initials: C
authors.lastname: Tschöpe
authors.forename: J W
authors.initials: JW
authors.lastname: Fischer
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D058578:Biglycan; D002921:Cicatrix; D016326:Extracellular Matrix Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D006342:Heart Rupture, Post-Infarction / Q000378:metabolism; D006439:Hemodynamics; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D011509:Proteoglycans / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: C546884:BGN protein, human; C546885:Bgn protein, mouse; D058578:Biglycan; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D012333:RNA, Messenger