title: Differential structural remodeling of the left-atrial posterior wall in patients affected by mitral regurgitation with or without persistent atrial fibrillation: a morphological and molecular study.
abstract: BACKGROUND
  Atrial fibrillation (AF) in mitral regurgitation (MR) is a complex disease where multiple factors may induce left-atrial structural remodeling (SR). We explored the differential SR of the left-atrial posterior wall (LAPW) of patients affected by MR with or without persistent AF, and the expression of key proteins involved in its pathogenesis.
  
  
  RESULTS
  Light microscopy of LAPW samples from 27 patients with MR and persistent AF (group 1), 33 with MR in sinus rhythm (group 2), and 15 autopsy controls (group 3) was used to measure myocyte diameter, percentage of myocytolytic myocytes, interstitial fibrosis, and capillary density; RT-PCR and Western blotting were used to assess the mRNA and protein levels of SOD-1, SOD-2, HO-1, calpain, MMP-2, MMP-9, TIMP-1, TIMP-2, and VEGF; immunofluorescence was used to locate these proteins. Myocyte diameter was similar in groups 1 and 2, but larger than controls. Compared to group 2, group 1 had more myocytolytic myocytes (20.8 ± 5.6% vs 14.7 ± 4.5%; P < 0.0001), increased interstitial fibrosis (10.4 ± 5.1% vs 7.5 ± 4.2%; P < 0.05), and decreased capillary density (923 ± 107 No/mm(2) vs 1,040 ± 100 No/mm(2); P < 0.0001). All of the proteins were more expressed in groups 1 and 2 than in controls. The protein and mRNA levels of SOD-1, SOD-2, MMP-2, and MMP-9 were higher in group 1 than in group 2.
  
  
  CONCLUSIONS
  The LAPW of MR patients with or without AF shows considerable SR. The former has more severe histopathological changes and higher levels of proteins involved in SR, thereby reaching a threshold beyond which the sinus impulse cannot normally activate atrial myocardium.
authors.affiliation: Department of Pathology and Laboratory Medicine, Section of Pathology, University of Parma, Parma, Italy. domenico.corradi@unipr.it
authors.forename: Domenico
authors.initials: D
authors.lastname: Corradi
authors.forename: Sergio
authors.initials: S
authors.lastname: Callegari
authors.forename: Roberta
authors.initials: R
authors.lastname: Maestri
authors.forename: David
authors.initials: D
authors.lastname: Ferrara
authors.forename: Domenica
authors.initials: D
authors.lastname: Mangieri
authors.forename: Rossella
authors.initials: R
authors.lastname: Alinovi
authors.forename: Paola
authors.initials: P
authors.lastname: Mozzoni
authors.forename: Silvana
authors.initials: S
authors.lastname: Pinelli
authors.forename: Matteo
authors.initials: M
authors.lastname: Goldoni
authors.forename: Ylenia Adelaide
authors.initials: YA
authors.lastname: Privitera
authors.forename: Veronica
authors.initials: V
authors.lastname: Bartoli
authors.forename: Ettore
authors.initials: E
authors.lastname: Astorri
authors.forename: Emilio
authors.initials: E
authors.lastname: Macchi
authors.forename: Augusto
authors.initials: A
authors.lastname: Vaglio
authors.forename: Stefano
authors.initials: S
authors.lastname: Benussi
authors.forename: Ottavio
authors.initials: O
authors.lastname: Alfieri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001146:Arrhythmia, Sinus / Q000503:physiopathology; D001281:Atrial Fibrillation / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D001344:Autopsy; D015153:Blotting, Western; D002154:Calpain / Q000378:metabolism; D018076:DNA, Complementary / Q000096:biosynthesis / Q000302:isolation & purification; D005260:Female; D005455:Fluorescent Antibody Technique; D006325:Heart Atria / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D018613:Microscopy, Confocal; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D002154:Calpain; D018076:DNA, Complementary; D020778:Matrix Metalloproteinase 2; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012313:RNA; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D042461:Vascular Endothelial Growth Factor A; D000099156:Superoxide Dismutase 2; C000606290:SOD1 protein, human