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Evidence for Mechanisms Underlying the Functional Benefits of a Myocardial Matrix Hydrogel for Post-MI Treatment.

ABSTRACT: BACKGROUND:There is increasing need for better therapies to prevent the development of heart failure after myocardial infarction (MI). An injectable hydrogel derived from decellularized porcine ventricular myocardium has been shown to halt the post-infarction progression of negative left ventricular remodeling and decline in cardiac function in both small and large animal models. OBJECTIVES:This study sought to elucidate the tissue-level mechanisms underlying the therapeutic benefits of myocardial matrix injection. METHODS:Myocardial matrix or saline was injected into infarcted myocardium 1 week after ischemia-reperfusion in Sprague-Dawley rats. Cardiac function was evaluated by magnetic resonance imaging and hemodynamic measurements at 5 weeks after injection. Whole transcriptome microarrays were performed on RNA isolated from the infarct at 3 days and 1 week after injection. Quantitative polymerase chain reaction and histologic quantification confirmed expression of key genes and their activation in altered pathways. RESULTS:Principal component analysis of the transcriptomes showed that samples collected from myocardial matrix-injected infarcts are distinct and cluster separately from saline-injected control subjects. Pathway analysis indicated that these differences are due to changes in several tissue processes that may contribute to improved cardiac healing after MI. Matrix-injected infarcted myocardium exhibits an altered inflammatory response, reduced cardiomyocyte apoptosis, enhanced infarct neovascularization, diminished cardiac hypertrophy and fibrosis, altered metabolic enzyme expression, increased cardiac transcription factor expression, and progenitor cell recruitment, along with improvements in global cardiac function and hemodynamics. CONCLUSIONS:These results indicate that the myocardial matrix alters several key pathways after MI creating a pro-regenerative environment, further demonstrating its promise as a potential post-MI therapy.

SUBMITTER: Wassenaar JW

PROVIDER: S-EPMC4779189 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Evidence for Mechanisms Underlying the Functional Benefits of a Myocardial Matrix Hydrogel for Post-MI Treatment.

Wassenaar Jean W JW Gaetani Roberto R Garcia Julian J JJ Braden Rebecca L RL Luo Colin G CG Huang Diane D DeMaria Anthony N AN Omens Jeffrey H JH Christman Karen L KL

Journal of the American College of Cardiology 20160301 9

<h4>Background</h4>There is increasing need for better therapies to prevent the development of heart failure after myocardial infarction (MI). An injectable hydrogel derived from decellularized porcine ventricular myocardium has been shown to halt the post-infarction progression of negative left ventricular remodeling and decline in cardiac function in both small and large animal models.<h4>Objectives</h4>This study sought to elucidate the tissue-level mechanisms underlying the therapeutic benef ...[more]

PMID: 26940929

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Project description:ObjectivesIn the setting of reperfused acute myocardial infarction (AMI), the authors sought to compare prediction of contractile recovery by infarct extracellular volume (ECV), as measured by T1-mapping cardiac magnetic resonance (CMR), with late gadolinium enhancement (LGE) transmural extent.BackgroundThe transmural extent of myocardial infarction as assessed by LGE CMR is a strong predictor of functional recovery, but accuracy of the technique may be reduced in AMI. ECV mapping by CMR can provide a continuous measure associated with the severity of tissue damage within infarcted myocardium.MethodsThirty-nine patients underwent acute (day 2) and convalescent (3 months) CMR scans following AMI. Cine imaging, tissue tagging, T2-weighted imaging, modified Look-Locker inversion T1 mapping natively and 15 min post-gadolinium-contrast administration, and LGE imaging were performed. The ability of acute infarct ECV and acute transmural extent of LGE to predict convalescent wall motion, ejection fraction (EF), and strain were compared per-segment and per-patient.ResultsPer-segment, acute ECV and LGE transmural extent were associated with convalescent wall motion score (p < 0.01; p < 0.01, respectively). ECV had higher accuracy than LGE extent to predict improved wall motion (area under receiver-operating characteristics curve 0.77 vs. 0.66; p = 0.02). Infarct ECV ≤0.5 had sensitivity 81% and specificity 65% for prediction of improvement in segmental function; LGE transmural extent ≤0.5 had sensitivity 61% and specificity 71%. Per-patient, ECV and LGE correlated with convalescent wall motion score (r = 0.45; p < 0.01; r = 0.41; p = 0.02, respectively) and convalescent EF (p < 0.01; p = 0.04). ECV and LGE extent were not significantly correlated (r = 0.34; p = 0.07). In multivariable linear regression analysis, acute infarct ECV was independently associated with convalescent infarct strain and EF (p = 0.03; p = 0.04), whereas LGE was not (p = 0.29; p = 0.24).ConclusionsAcute infarct ECV in reperfused AMI can complement LGE assessment as an additional predictor of regional and global LV functional recovery that is independent of transmural extent of infarction.

Dataset Information

Evidence for Mechanisms Underlying the Functional Benefits of a Myocardial Matrix Hydrogel for Post-MI Treatment.

Publications

Evidence for Mechanisms Underlying the Functional Benefits of a Myocardial Matrix Hydrogel for Post-MI Treatment.

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