التفاصيل البيبلوغرافية
| العنوان: |
Delivery of a matrix metalloproteinase-responsive hydrogel releasing TIMP-3 after myocardial infarction: effects on left ventricular remodeling. |
| المؤلفون: |
Purcell, Brendan P.1, Barlow, Shayne C.2, Perreault, Paige E.2, Freeburg, Lisa2, Doviak, Heather2, Jacobs, Julia2, Hoenes, Abigail2, Zellars, Kia N.2, Khakoo, Aarif Y.3, Lee, TaeWeon3, Burdick, Jason A.1, Spinale, Francis G.2 cvctrc@uscmed.sc.edu |
| المصدر: |
American Journal of Physiology: Heart & Circulatory Physiology. Oct2018, Vol. 315 Issue 4, pH814-H825. 12p. |
| مصطلحات موضوعية: |
*MATRIX metalloproteinase inhibitors, *VENTRICULAR remodeling, *MYOCARDIAL infarction, *SALINE injections, *HEART failure, *MATRIX metalloproteinases |
| مصطلحات جغرافية: |
MICHIGAN |
| مستخلص: |
Although improvements in timing and approach for early reperfusion with acute coronary syndromes have occurred, myocardial injury culminating in a myocardial infarction (MI) remains a common event. Although a multifactorial process, an imbalance between the induction of proteolytic pathways, such as matrix metalloproteinases (MMPs) and endogenous tissue inhibitors of metalloproteinase (TIMPs), has been shown to contribute to this process. In the present study, a full-length TIMP-3 recombinant protein (rTIMP-3) was encapsulated in a specifically formulated hyaluronic acid (HA)-based hydrogel that contained MMP-cleavable peptide cross-links, which influenced the rate of rTIMP-3 release from the HA gel. The effects of localized delivery of this MMP-sensitive HA gel (HAMMPS) alone and containing rTIMP-3 (HAMMPS/rTIMP-3) were examined in terms of the natural history of post-MI remodeling. Pigs were randomized to one of the following three different groups: MI and saline injection (MI/saline group, 100-µl injection at nine injection sites, n = 7), MI and HAMMPS injection (MI/HAMMPS group; 100-µl injection at nine injection sites, n = 7), and MI and HAMMPS/rTIMP-3 injection (MI/HAMMPS/rTIMP-3 group; 20-µg/100-µl injection at nine injection sites, n = 7). Left ventricular (LV) echocardiography was serially performed up to 28 days post-MI. LV dilation, as measured by end-diastolic volume, and the degree of MI wall thinning were reduced by ~50% in the HAMMPS/rTIMP-3 group (P < 0.05). Furthermore, indexes of heart failure progression post-MI, such as LV filling pressures and left atrial size, were also attenuated to the greatest degree in the HAMMPS/rTIMP-3 group. At 28 days post-MI, HAMMPS/rTIMP-3 caused a relative reduction in the transcriptional profile for myofibroblasts as well as profibrotic pathways, which was confirmed by subsequent histochemistry. In conclusion, these findings suggest that localized delivery of a MMP-sensitive biomaterial that releases a recombinant TIMP holds promise as a means to interrupt adverse post-MI remodeling. [ABSTRACT FROM AUTHOR] |
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