Delivery of a matrix metalloproteinase-responsive hydrogel releasing TIMP-3 after myocardial infarction: effects on left ventricular remodeling.

Despite the improvements in time and approach to early reperfusion in acute coronary syndromes occur, culminating myocardial injury in myocardial infarction (MI) remains a common event. Despite the multifactorial process, the imbalance between the induction of proteolytic pathways, such as matrix metalloproteinases (MMPs) and endogenous tissue inhibitors Ovine Recombinant Proteins of metalloproteinases (TIMPs), have been shown to contribute to this process. 

In this study, a full-length recombinant TIMP-3 protein (rTIMP-3) are packed in a specially formulated hyaluronic acid (HA) based hydrogel containing MMP-cleavable peptide cross-links, which affects the level of rTIMP- 3 release of the HA gel , Effects of local delivery of MMP-sensitive HA this gel (HAMMPS) alone and contains rTIMP-3 (HAMMPS / rTIMP-3) examined in terms of the natural history of post-MI remodeling. 

Pigs were randomized to one of the following three distinct groups: MI and injection of saline (MI / saline group, the injection of 100 ml in nine locations injection, n = 7), MI and HAMMPS injection (group MI / HAMMPS; injection 100-ml at nine locations injection, n = 7), and MI and HAMMPS / rTIMP 3rd injection (MI / HAMMPS / rTIMP-3 group; injection of 20 mg / 100 ml at nine locations injection, n = 7). 

Left ventricular (LV) serial echocardiography was performed up to 28 days post-MI. LV dilation, as measured by the end-diastolic volume and wall thinning rate of MI was reduced ~ 50% in the group HAMMPS / rTIMP-3 (P <0.05). In addition, an index of development of post-MI heart failure, such as LV filling pressure and left atrial size, too attenuated to the greatest degree in the group HAMMPS / rTIMP-3. At 28 days post-MI, HAMMPS / rTIMP-3 led to a relative reduction in transcription profiles of myofibroblasts and profibrotic pathway, which was confirmed by subsequent histochemistry. 

In conclusion, these findings suggest that local delivery of MMP-sensitive biomaterial that releases a recombinant TIMP holds promise as a means to interrupt adverse post-MI remodeling. New & Noteworthy This study targeted proteolytic system http://gentaur-antibodies.com/ of myocardial matrix, the matrix metalloproteinases (MMPs), through the  using use of recombinant tissue inhibitors of MMPs put in MMP-sensitive hydrogel, which regional injecteda large animal model of myocardial infarction.

Leaving ventricular geometry and function and myocardial remodeling indices improved with this approach and supporting the advancement of local therapeutic strategies that specifically target myocardial matrix.