Low MMP-8/TIMP-1 reflects left ventricle impairment in takotsubo cardiomyopathy and high TIMP-1 may help to differentiate it from acute coronary syndrome.

Abstract

BACKGROUND:

Matrix metalloproteinase 8 (MMP-8) is the most potent type-I collagen protease. Such collagen mainly constitutes the transient fibrosis in takotsubo cardiomyopathy (TTC) endomyocardial biopsies. High MMP-8 and tissue-inhibitor of matrix metalloproteinase-1 (TIMP-1) levels are implicated in acute coronary syndrome (ACS). We compared MMP-8 and TIMP-1 levels in consecutive TTC and ACS patients, and their association to TTC severity.

METHODS AND RESULTS:

In 45 acute serum samples of TTC, 2072 ACS and 1000 controls, TIMP-1 differed between ACS 146.7ng/mL (115.0-186.3) (median (interquartile range)), TTC 115.7 (94.3-137.7) and controls 80.9 (73.2-90.4), (p<0.0001). MMP-8 levels were similar between ACS and TTC. In receiver-operating characteristics analysis, TIMP-1 differentiated TTC from ACS with an area under the curve (AUC) of 0.679 (p<0.0001) surpassing troponin T (TnT) at 0.522 (p = 0.66). Compared to other differing factors (age, sex, smoking), TIMP-1 improved diagnostic specificity and sensitivity from AUC of 0.821 to 0.844 (p = 0.007). The MMP8/TIMP-1 molar ratio differentiated normal ejection fraction (EF) at 0.27 (0.13-0.51) from decreased EF<50% at 0.08 (0.05-0.20), (p = 0.04) in TTC, but not in ACS.

CONCLUSIONS:

Even with other differing factors considered, TIMP-1 differentiated TTC from ACS better than TnT. In TTC, the low MMP-8/TIMP-1 molar ratio may reflect decreased proteolysis and increased transient fibrosis, perhaps in part explaining the left-ventricle impairment.

• Authors: Olavi Parkkonen, Mikko T Nieminen, Paula Vesterinen, Taina Tervahartiala, Markus Perola, Veikko Salomaa, Pekka Jousilahti, Timo Sorsa, Pirkko J Pussinen, Juha Sinisalo
• Journal: PloS one (PLoS One) Vol. 12 Issue 3 Pg. e0173371 ( 2017) ISSN: 1932-6203 [Electronic] United States
• PMID: 28278213 (Publication Type: Journal Article)

Chemical References

• Tissue Inhibitor of Metalloproteinase-1
• Matrix Metalloproteinase 8

Topics

• Acute Coronary Syndrome (blood, diagnosis)
• Adult
• Aged
• Diagnosis, Differential
• Female
• Humans
• Male
• Matrix Metalloproteinase 8 (blood)
• Myocardial Contraction
• Takotsubo Cardiomyopathy (blood, diagnosis, enzymology, physiopathology)
• Tissue Inhibitor of Metalloproteinase-1 (blood)
• Ventricular Dysfunction, Left