Type-specific dysregulation of matrix metalloproteinases and their tissue inhibitors in end-stage heart failure patients: relationship between MMP-10 and LV remodelling.
Although past studies observed the changes of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in end-stage heart failure (HF) patients, a consistent and clear pattern of type-specific MMPs and/or TIMPs has yet to be further defined. In this study, proteomic approach of human protein antibody arrays was used to compare MMP and TIMP expression levels of left ventricular (LV) myocardial samples from end-stage HF patients due to dilated cardiomyopathy (DCM) with those from age- and sex- matched non-failing patients. Western blot analysis, immunohistochemistry and ELISA were used for validation of our results. We observed that MMP-10 and -7 abundance increased, accompanied by decreased TIMP-4 in DCM failing hearts (n= 8) compared with non-failing hearts (n= 8). The results were further validated in a cohort of 34 end-stage HF patients derived from three forms of cardiomyopathies. Cardiac and plasma MMP-10 levels were positively correlated with the LV end-diastolic dimension in this HF cohort. In addition, we observed that insulin-like growth factor-2 promoted MMP-10 production in neonatal rat cardiomyocytes. In conclusion, this study demonstrated a selective up-regulation of MMP-10 and -7 along with a discordant change of TIMP-4, and a positive correlation between MMP-10 levels and the degree of LV dilation in end-stage HF patients. Our findings suggest that type-specific dysregulation of MMPs and TIMPs is associated with LV remodelling in end-stage HF patients, and MMP-10 may act as a novel biomarker for LV remodelling.
Wei
Yingjie
Y
Chinese Academy of Medical Sciences, Peking Union Medical College, Fuwai Hospital & Cardiovascular Institute, Key Laboratory of Cardiovascular Regenerative Medicine, Ministry of Health, Beijing, PR China. weiyingjiefw@126.com
Cui
Chuanjue
C
Lainscak
Mitja
M
Zhang
Xiaoling
X
Li
Jun
J
Huang
Jie
J
Zhang
Hao
H
Zheng
Zhe
Z
Hu
Shengshou
S
D000293:Adolescent; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000201:enzymology / Q000503:physiopathology; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000201:enzymology* / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D008297:Male; D053506:Matrix Metalloproteinase 10 / Q000097:blood / Q000378:metabolism*; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D051381:Rats; D015203:Reproducibility of Results; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology*; D000097792:Tissue Inhibitor of Metalloproteinase-4
D007335:Insulin-Like Growth Factor II; D053506:Matrix Metalloproteinase 10; D020783:Matrix Metalloproteinase 7; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4; C511770:MMP10 protein, human; C060932:MMP7 protein, human