The System of Neutrophil Elastase and the Plasma Level of MMP-7 in Children with Pulmonary Arterial Hypertension and Chronic Cor Pulmonale

PROBLEMS OF PEDIATRICS
Еlena M. Vasilyeva, PhD, ScD¹; Кirill A. Zykov, PhD, ScD²; Мichael I. Bakanov, PhD, ScD¹; Аnna O. Bogatyreva, PhD²; Anna V. Rvacheva, PhD²; Victoria B. Beilina, PhD²; Tatiana V. Kuznetzova, PhD² ; Olga I. Simonova, PhD, ScD¹; Yulia V. Solovjeva, Ph

¹Scientific Center for Children’s Health RAMS; ²Moscow State Medical Stomatological University; Moscow, Russian Federation

*Corresponding author: Еlena M. Vasilyeva PhD, ScD, Laboratory of Clinical Biochemistry, Scientific Center for Children’s Health of Russian Academy of Medical Sciences, 2/62, Lomonosov ave., Moscow, 117963, Russia. Tel: 7-499-1254954. E-mail: Elena-vasilieva-44@yandex.ru

Published: December 25, 2013 

Abstract: 

A significant increase in the activity of neutrophil elastase (NE) and anti-NE-protection in the plasma were detected in children having bronchopulmonary dysplasia (BPD) complicated by pulmonary arterial hypertension (PAH) and chronic cor pulmonale (CCP). The changes revealed were more pronounced in patients with CCP. The plasma concentration of the NE was slightly reduced, which was probably associated with the activation of anti-NE and an increase in the α1-antitrypsin level. A gradual increase was noted in the plasma level of the matrix metalloproteinase-7 (MMP-7) in patients with an increase in the severity of the condition. In patients with cystic fibrosis (with and without CCP), the pronounced increase in the MMP-7 level was observed. In patients with cystic fibrosis (CF), even without the additional complication with PAH and CCP, the MMP-7 level was significantly higher than in those with congenital broncho-pulmonary malformations (CBPM).  The difference was increased in those patients with PAH and reached a maximum in those with CCP.

Keywords: 
neutrophil elastase; matrix metalloproteinase-7; bronchopulmonary dysplasia; pulmonary arterial hypertension; chronic cor pulmonale.
References: 
  1. Galiè N, Torbicki A, Barst R, Dartevelle P, Haworth S, Higenbottam T,  et al.  Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Eur Heart J 2004; 25(24): 2243-78.
  2. Dubinina EE, Pustygina AA. Free radical processes in aging, neurodegenerative diseases and other pathological states. Biomed Chemistry 2007; 53(4):351-372. [Article in Russian].
  3. Greene CM, McElvaney NG. Proteases and antiproteases in chronic neutrophilic lung disease – relevance to drag discovery. Br J Pharmacol  2009; 158(4):1048-58.
  4. Taggart CC, Greene CM, Carroll TP, O'Neill SJ, McElvaney NG.  Elastolytic proteases: inflammation resolution and dysregulation in chronic infective lung disease. Am J Respir Crit Care Med 2005; 171(10):1070-6.
  5. Goncharova NS, Moiseeva  OM,  Shlyakhto EV, Aleshin GM.  Matrix metalloproteinases:  value in myocardial remodeling in valvular heart disease. Kardiologiia 2007; 12:49-52. [Article in Russian].
  6.  Parks WC, Shapiro SD. Matrix metalloproteinases in lung biology. Respir Res 2001; 2(1):10-9.
  7.  Efremenko YR. Proteolytic enzymes: a highly sensitive criterion for efficacy and safety. Biomed Chemistry 2008; 54(2):179-83. [Article in Russian].
  8. Barnes PJ, Shapiro SD, Pauwels RA. Chronic obstructive pulmonary disease: molecular and cellular mechanisms. Eur Respir J 2003; 22(4):672-88.
  9. Bergin DA, Reeves EP, Meleady P, Henry M, McElvaney OJ, Carroll TP, et al.  α-1 antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8.  J Clin Invest 2010; 120(12): 4236-50.
  10.  Petrache I, Fijalkowska I, Medler TR, Skirball J, Cruz P, Zhen L, et al. a1-antitrypsin inhibits caspase-3 activity, preventing lung endothelial cell apoptosis. Am J of Pathol 2006; 169(4):155-66.        
  11.  Boudier C, Holle C, Bieth JG. Stimulation of the elastolytic activity of leukocyte elastase by leukocyte catepsin G. J Biol Chem 1981; 256(20): 10256-8.
  12.  Myagkova MA. Natural antibodies to low molecular compounds. Мoscow: LMSU; 2001.
  13.  Parks WC. Matrix metalloproteinases in lung repair. Eur Respir J 2003; 22 (Suppl 44): 36s-38s.
  14.  Winkler MK, Foldes JK, Bunn RC, Fowlkes JL. Implications for matrix metalloproteinases as modulators of pediatric lung disease. Am J Physiol Lung Cell Mol Physiol 2003; 284(4):L557-65.
  15.  Vandivier RW, Fadok VA, Hoffmann PR, Bratton DL, Penvari C, Brown KK, et al. Elastase-mediated phosphatidylserine receptor cleavage impairs apoptotic cell clearance in cystic fibrosis and bronchiectasis. J Clin Invest 2002; 109(5):661-70.               

The fully formatted PDF version is available.

Download Article

Int J Biomed. 2013; 3(4):269-273. © 2013 International Medical Research and Development Corporation. All rights reserved.