Signaling Pathways in Cardiovascular Development

Marı́n-Garcı́a, José

doi:10.1007/978-1-4419-9461-5_9

Cited by 1 publication

(1 citation statement)

References 345 publications

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“…We found increased expression of 6 cardiac transcription factors. Of these, GATA4, myocardin, Nkx2.5, Tbx5, and Tbx20 are all expressed throughout various stages of embryonic cardiogenesis (29), while GATA4, Nkx2.5, and Tbx5 are frequently used to identify various CPC subsets (30). Increased expression of MEF and GATA4 were reported following injection of bone marrow cells and mononuclear cell secretomes (10,13); however, to our knowledge, concomitant elevated transcription of several cardiac transcription factors has not been previously reported.…”

Section: Discussionmentioning

confidence: 99%

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

Wassenaar

Gaetani

Garcia

et al. 2016

Journal of the American College of Cardiology

132

117

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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 We 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 post-injection. Whole transcriptome microarrays were performed on ribonucleic acid (RNA) isolated from the infarct at 3 days and 1 week after injection. Quantitative polymerase chain reaction and histological 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 controls. Pathway analysis indicated that these differences are due to changes in several tissue processes that may contribute to improved cardiac healing post-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 post-MI creating a pro-regenerative environment, further demonstrating its promise as a potential post-MI therapy.

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