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Both collagen and elastin matrices are remodeled in the failing ovine atria – a role for elastin‐degrading enzymes in atrial structural remodeling
Author(s) -
Horn Margaux A,
Graham Helen K,
Borland Samantha J,
Clarke Jessica D,
Dibb Katharine M,
Trafford Andrew W
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1129.7
Subject(s) - elastin , extracellular matrix , sirius red , zymography , matrix metalloproteinase , fibrosis , medicine , chemistry , gelatinase , lysyl oxidase , endocrinology , pathology , biochemistry
Left atrial (LA) remodeling is a feature of the full spectrum of heart failure (HF) and LA structural remodeling (fibrosis) will contribute to diminished ventricular contractile function and risk of atrial fibrillation. Whilst the fibrotic potential of the LA in HF has been documented, the mechanism by which this occurs, and the role of other matrix proteins is less well understood. HF was induced in female sheep by rapid ventricular pacing. LA dilatation was present in symptomatic animals as measured by echocardiography. Paraffin embedded tissue sections from the left auricle were stained with picro‐sirius red or Millers stain for quantification of collagen and elastin, respectively. Microscopy revealed both elastic, and collagenous components and in HF, collagen:elastin ratio was increased. Gelatinase activity was measured by zymography and protein levels of the elastin‐degrading MMP ‐3, TIMPs 1–4 and secreted protein acidic and rich in cysteine (SPARC) were measured by immunoblotting. MMP‐2 activity, MMP‐3 and SPARC proteins were increased after rapid pacing, whereas levels TIMP‐1 were decreased. Both collagen and elastin networks are altered in the ovine LA in HF which is likely to contribute towards a stiffer, less compliant phenotype. Changes to different MMP profiles in failing atria may provide a mechanism for this atrial extracellular matrix remodeling. Work was funded by the BHF.