Circulating biomarkers of tissue remodelling in pulmonary hypertension.
OBJECTIVE
Besides persisting high pulmonary arterial pressure and increased pulmonary vascular resistance, remodelling of pulmonary tissues and subsequently the right heart are the key pathomechanisms of pulmonary hypertension (PH). Extracellular matrix maintenance in this context plays a central role.


METHODS
We tested the hypothesis that plasma concentration of matrix metalloproteinase (MMP)-2, tissue inhibitor of matrix metalloproteinases (TIMP)-4 and tenascin C (TNC) might be useful as biomarkers for assessing the severity of PH. Therefore, the concentrations of MMP-2, TIMP-4, TNC and N-terminal b-type natriuretic peptide (NT-proBNP) of 36 PH patients were compared with those of 44 age- and gender-matched healthy volunteers. Additionally, lung function, 6-min walk distance and right heart function were assessed.


RESULTS
In PH patients, significantly elevated plasma levels of MMP-2, TIMP-4, TNC and NT-proBNP were detected. In particular, TIMP-4 was significantly increased in patients with higher NYHA classification, and in patients with severe right ventricular hypertrophy.


CONCLUSIONS
Monitoring of plasma TIMP-4 and to a lesser extent of MMP-2 and TNC levels in PH patients might help to assess the beneficial effects of PH pharmacotherapy on tissue remodelling.
Clinic of Internal Medicine II, University of Ulm, Ulm, Germany.
Christian
C
Schumann
Philipp M
PM
Lepper
Hedwig
H
Frank
Roland
R
Schneiderbauer
Thomas
T
Wibmer
Cornelia
C
Kropf
Kathrin M
KM
Stoiber
Stefan
S
Rüdiger
Lothar
L
Kruska
Thomas
T
Krahn
Frank
F
Kramer
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D006328:Cardiac Catheterization; D004452:Echocardiography; D005080:Exercise Test; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000473:pathology*; D007118:Immunoassay; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D012129:Respiratory Function Tests; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood; D048069:Tumor Necrosis Factors / Q000097:blood; D016138:Walking / Q000502:physiology; D000097792:Tissue Inhibitor of Metalloproteinase-4
D015415:Biomarkers; D020778:Matrix Metalloproteinase 2; D020097:Natriuretic Peptide, Brain; D010446:Peptide Fragments; D019714:Tissue Inhibitor of Metalloproteinases; D048069:Tumor Necrosis Factors; D000097792:Tissue Inhibitor of Metalloproteinase-4; C109794:pro-brain natriuretic peptide (1-76)