Imbalance of Matrix Metalloproteinases/Tissue Inhibitor of Metalloproteinase-1 and Loss of Fibronectin Expression in Patients with Congestive Heart Failure

Cardiology ◽  
2010 ◽  
Vol 116 (2) ◽  
pp. 133-141 ◽  
Author(s):  
Da-chun Yang ◽  
Shuang-tao Ma ◽  
Yan Tan ◽  
Yi-hua Chen ◽  
De Li ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Matrix Metalloproteinases ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Tissue Inhibitor ◽  
Fibronectin Expression

Abstract 065: Cardiac Fibrosis and Heart Failure Caused by DsRed Tetramers Involves the Induction of Tissue Inhibitor of Metalloproteinase-1

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Tsung-Hsien Chen ◽  
Shan-Wen Liu ◽  
Mei-Ru Chen ◽  
Kurt M Lin
Keyword(s):  
Heart Failure ◽  
Cardiac Fibrosis ◽  
Fluorescent Protein ◽  
Early Stage ◽  
Transglutaminase 2 ◽  
Underlying Mechanism ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Tissue Inhibitor ◽  
Cardiac Tissues ◽  
Cardiac Symptoms

Whereas aggregation of intracellular proteins was linked to the initiation of cardiac myopathy, the sequence of participating events, including myocyte apoptosis, autophagy, necrosis and fibrosis as the underlying mechanisms leading to heart failure, was not clear. Green fluorescent protein (GFP) and its derivatives induced cardiac dysfunction in mice when expressed in high quantity; however, the mechanism underlying the aggregation of fluorescent protein leading to heart failure remains unexplored.We created a transgenic mouse with switchable expression of the GFP monomer or the expression of DsRed, a red fluorescent protein (RFP) tetramer that tends to aggregate into a large protein complex. GFP mice were free of cardiac symptoms; in contrast, RFP mice with homozygous DsRed alleles developed myocyte necrosis, carditis, ventricular hypertrophy and fibrosis, left atrium thrombosis, dilated heart failure and death at the age of approximately five months. The hemizygote mice displayed similar symptoms at a later age. The expression of the microtubule-associated protein 1 light chain 3 cleaved isoform II (LC3 II) and transglutaminase 2, and the expression of many myopathy- and fibrosis-related genes were significantly induced in the hearts of two-month-old RFP mice. Together with the findings of increased autophagosomes, lysosomes and dysfunctional mitochondria, these results suggest a marked induction of myocyte autophagy and fibrosis as the main underlying mechanism of heart failure in RFP mice. Interestingly, apoptosis was not elevated in RFP hearts. One of the most up-regulated genes in the early stage RFP heart was the tissue inhibitor of matrix metalloproteinases type 1 (TIMP-1), corroborating the role of TIMP-1 in cardiac remodeling and anti-apoptotic activity. The heart-origin of the morbidity in RFP mice was confirmed by expressing DsRed tetramers specifically in cardiac tissues, and the same phenotypes as in RFP mice were observed. In summary, in cardiac myocytes under the stress of protein aggregation, strong induction of TIMP-1 and down-regulation of MMP activity may play a significant role in enhancing the synthesis of extracellular matrix, resulting in fibrosis and heart failure.

Increased Levels of Tissue Inhibitor of Metalloproteinase 1 (TIMP-1) Are Independently Associated with Adverse Outcomes in Outpatients with Heart Failure

2010 ◽  
Vol 16 (8) ◽  
pp. S32-S33
Author(s):  
Vasiliki V. Georgiopoulou ◽  
Andreas P. Kalogeropoulos ◽  
Grigorios Giamouzis ◽  
Lucy Fike ◽  
Kunal Bhatt ◽  
...  
Keyword(s):  
Heart Failure ◽  
Adverse Outcomes ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Tissue Inhibitor

Reduction in levels of matrix metalloproteinases and increased expression of tissue inhibitor of metalloproteinase—2 in response to mild hypothermia therapy in experimental stroke

2005 ◽  
Vol 103 (2) ◽  
pp. 289-297 ◽  
Author(s):  
Jong Eun Lee ◽  
Yone Jung Yoon ◽  
Michael E. Moseley ◽  
Midori A. Yenari
Keyword(s):  
Matrix Metalloproteinases ◽  
Matrix Metalloproteinase ◽  
Mild Hypothermia ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Matrix Metalloproteinase 2 ◽  
Experimental Stroke ◽  
Tissue Inhibitor ◽  
Content Type ◽  
The Brain ◽  
Fine Print

Object. Mild hypothermia is a robust neuroprotectant, and the results of prospective clinical trials have indicated that it may improve neurological outcome in certain instances. One aspect of this protection has been associated with the prevention of blood—brain barrier (BBB) disruption. Matrix metalloproteinases (MMPs) have been implicated in BBB disruption because they can degrade the extracellular matrix. In this study the authors explored the relationship between hypothermia and MMPs and whether BBB preservation resulting from mild hypothermia therapy is due to alterations in MMP expression. Methods. Rats were subjected to middle cerebral artery occlusion for 2 hours; the animals were maintained in a state of normothermia or mild hypothermia (33°C) immediately after the onset of ischemia. The animals' brains were collected 2, 6, and 24 hours after ischemia began. Contrast-enhanced T1-weighted magnetic resonance imaging was performed at 24 hours to assess the extent of BBB disruption. Consistent with prior reports, areas of BBB disruption detected on T1-weighted images were smaller in the brains of rats maintained in a state of hypothermia (normothermia group 8.6 ± 3% of the brain; hypothermia group 0.2 ± 0.1% of the brain; p < 0.01). Expression of both MMP-2 and MMP-9 at the transcriptional and translational levels was reduced in hypothermic brains at 6 hours and 24 hours after ischemic injury. Matrix metalloproteinase—9 was primarily localized to cells of monocytic origin but was also observed in neurons and astrocytes. Matrix metalloproteinase—2 was found in some neurons and astrocytes but not in inflammatory cells. In addition, hypothermia increased the levels of the endogenous MMP inhibitor, tissue inhibitor of metalloproteinases—2. Conclusions. The authors conclude that mild hypothermia attenuates BBB disruption, decreases MMP expression, and suppresses MMP activity.

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