Expression and complex formation of MMP9, MMP2, NGAL, and TIMP1 in porcine myocardium but not in skeletal muscles in male pigs with tachycardia-induced systolic heart failure

Biomed Res Int. 2013:2013:283856. doi: 10.1155/2013/283856. Epub 2013 Apr 22.

Abstract

Matrix metalloproteinases (MMPs) are involved in the remodeling of extracellular matrix in various tissues. Their functioning could be related to the formation of complexes, containing MMP9, MMP2, tissue inhibitor of metalloproteinases type 1 (TIMP1), and neutrophil gelatinase-associated lipocalin (NGAL). Such complexes have not been investigated in either myocardial or skeletal muscles. We examined 20 male pigs with heart failure (HF), and 5 sham-operated animals. There were no differences in the mRNA expression of MMP9, MMP2, TIMP1, and NGAL between diseased and healthy animals, in either left ventricle (LV) myocardium or skeletal muscles. In LV from both diseased and healthy animals, in nonreducing and nondenaturing conditions, we demonstrated the presence of high molecular weight (HMW) complexes (130, 170, and 220 kDa) containing MMP9, TIMP1, and NGAL (also MMP2 in 220 kDa complex) without proteolytic activity, and a proteolytically active 115 kDa MMP9 form together with 72 and 68 kDa bands (proMMP2 and MMP2). Proteolytically active bands were also spontaneously released from HMW complexes. In skeletal muscles from both diseased and healthy animals, in nonreducing and nondenaturing conditions, we found no HMW complexes, and proteolytic activity was associated with the presence of 72 and 68 kDa bands (proMMP2 and MMP2).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / biosynthesis
  • Animals
  • Disease Models, Animal
  • Gene Expression Regulation
  • Heart Failure, Systolic / complications
  • Heart Failure, Systolic / genetics*
  • Heart Failure, Systolic / metabolism
  • Heart Failure, Systolic / pathology
  • Humans
  • Lipocalin-2
  • Lipocalins / biosynthesis
  • Male
  • Matrix Metalloproteinase 2 / biosynthesis*
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Matrix Metalloproteinase 9 / metabolism
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Proto-Oncogene Proteins / biosynthesis
  • Swine / genetics
  • Swine / metabolism
  • Tachycardia / complications
  • Tachycardia / metabolism
  • Tachycardia / pathology
  • Tissue Inhibitor of Metalloproteinase-1 / biosynthesis*
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism

Substances

  • Acute-Phase Proteins
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Multiprotein Complexes
  • Proto-Oncogene Proteins
  • Tissue Inhibitor of Metalloproteinase-1
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9