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We read with great interest the article by Nagpal and coworkers,1 who revealed a critical role of miR-125b for the induction of cardiac fibrosis by promoting the proliferation and activation of cardiac fibroblasts through inhibition of the p53 signaling pathway in fibroblasts. They further showed that in vivo silencing of miR-125b by systemic delivery of locked nucleic acid prevented angiotensin II–induced cardiac fibrosis, which indicates that miR-125b is important for the development of hypertensive cardiac fibrosis. Although this novel discovery opens the door for new treatment of cardiac fibrosis, it is not known whether miR-125b is cell specific and whether the locked nucleic acid …

We read with great interest the article by Li et al,1 who demonstrated that the upregulation of ATF3, a cardiac fibroblast–enriched transcription factor, is cardioprotective against hypertensive fibrosis via suppression of Map2K3 expression and p38 MAPK signaling. Specifically, they showed that ATF3 is upregulated in cardiac fibroblasts but not in cardiomyocytes from hypertensive animals and patients with heart failure. ATF3 knockout exaggerated whereas ATF3 overexpression ameliorated ventricular remodeling in hypertensive mice. Their data strongly suggest that upregulation of ATF3 in cardiac fibroblasts is a self-compensatory protective mechanism against ventricular remodeling associated with heart failure. It is important …

We read with great interest the important article by Sayed and coworkers1 on the role of innate immunity in somatic reprogramming. They discovered that activation of innate immune signaling by small molecules and an agonist of Toll-like receptor 3, combined with endothelial growth factors, is sufficient to transdifferentiate human fibroblasts to endothelial cells. The same research group reported previously that stimulation of Toll-like receptor 3 causes global changes in the expression of epigenetic modifiers to enhance nuclear reprogramming.2 …

We read with great interest the article by Ong et al,1 who demonstrated that codelivery of cardiac progenitor cells (CPCs) with a minicircle plasmid carrying hypoxia-inducible factor-1 into the ischemic myocardium can improve the survival of transplanted CPCs. Their data revealed that hypoxia-inducible factor-1 was able to modulate the local niche and transform it from a hostile ischemic milieu into a hospitable environment for transplanted stem cells. Specifically, they showed that minicircle plasmid carrying hypoxia-inducible factor-1 was taken up by cardiac endothelial cells, which secreted exosomes that were internalized by the CPCs. The …

We read with great interest the article by D’Amario et al1 about the growth characteristics of cardiac stem cells (CSCs), which can be used as an indicator of positive left ventricular remodeling in the heart after surgery. Although animal and clinical studies have demonstrated that CSCs have regenerative potential to repair injured myocardium,2 this is the first …

We read with great interest of the article by Liu and coworkers1 about master epigenetic regulator, ten-eleven translocation-2 (TET2), regulating smooth muscle cell (SMC) plasticity. TET2 is 1 of very recently discovered DNA demethylases which oxidizes 5-methylcytosine (5-mC) to generate 5-hydroxymethylcytosine (5-hmC). Liu et al discovered that TET2 knockdown prevents rapamycin-induced SMC differentiation, whereas TET2 overexpression is sufficient to induce SMC contractile phenotype. Notably, they found that ectopic expression of TET2 is sufficient to direct SMC differentiation from fibroblasts. To our knowledge, this is the first report …

Persistent hyperglycemia represents a major metabolic complication of diabetes, which may cause endothelial cell dysfunction and apoptosis. microRNAs are novel biomarkers, modulators and therapeutic targets for disease. The microRNA miR-221 is expressed in human umbilical vein endothelial cells (HUVEC). Insulin-like growth factor 1 (IGF-1) is an important survival factor for multiple cell types. This study was to investigate whether high glucose (HG) induces endothelial dysfunction and apoptosis through altering the microRNA expression and IGF-1 signaling. The mirVana qRT-PCR miRNA detection assay showed that exposure to glucose for 24 h dose-dependently (up to 25 mM) increased miR-221 expression by 2.6 ± 0.5 folds (p This research has received full or partial funding support from the American Heart Association, AHA South Central Affiliate (Arkansas, New Mexico, Oklahoma & Texas).

Mesenchymal stem cells (MSCs) contribute myocardial regeneration, and the beneficial effects may be mediated by paracrine factors produced by MSCs. C-kit positive neonatal cardiomyocytes (NCMs) contribute to myocardial regeneration, but they do not give a robust regenerative response since low expression of c-kit. Cell-cycle reentry of NCMs and insulin-like growth factor (IGF-1) improve myocardial function in infarcted hearts. MSCs and NCMs were prepared from Lewis rats, and cocultured in two chambers which allowed the diffusion of secreted factors from upper chamber to lower chamber, but prevented cell contacts. MSCs secreted significant amount of IGF-1 (159.6 ± 34.4 pg/ug DNA at 24 h, 285.3 ± 28.5 pg/ug DNA at 48 h, and 358.3 ± 39.9 pg/ug DNA at 72 h), whereas the amount of IGF-1 in conditioned medium from NCMs was undetectable assessed by IGF-1 ELISA. Using flow cytometry, we found that the secreted factors by MSCs increased c-kit protein expression, which was attenuated by IGF-1 receptor neutralizing antibody (IGF-1R Ab) and phosphatidylinositol 3 (PI3) kinase inhibitor LY 294002 (NCM vs MSC/NCM vs MSC/NCM+IGF-1R Ab vs MSC/NCM+ LY294002= 1.5 ± 0.6 % vs 5.5 ± 0.3 % vs 1.9 ± 0.6% vs 2.1 ± 0.5%) assessed by flow cytometry. The cytokinesis of NCMs was increased when cocultured with MSC analyzed by calcein fluorescence intensity (3.1 ± 0.5 fold increase, p This research has received full or partial funding support from the American Heart Association, AHA South Central Affiliate (Arkansas, New Mexico, Oklahoma & Texas).