Self-Assembling Peptide Nanofibers for MMP Delivery and Cardiac Regeneration in Diabetes

2011 ◽  
Author(s):  
Jennifer R. Hurley ◽  
Abdul Q. Sheikh ◽  
Meredith Beckenhaupt ◽  
Cameron Ingram ◽  
Andrew Mutchler ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Cardiac Regeneration ◽  
The United States ◽  
Matrix Remodeling ◽  
Self Assembling ◽  
Peptide Nanofibers ◽  
Novel Target

Diabetes is a serious problem in the United States, afflicting 7.8% of the population with annual medical costs estimated at $116B in 2007 (1). Diabetic cardiomyopathy (DCM) is a cardiovascular complication of diabetes resulting in pathological alterations to the myocardium including circulatory defects, impaired heart muscle contraction, and progressive fibrosis. Cardiac fibrosis is associated with an imbalance between the deposition of the extracellular matrix (ECM) proteins by cardiac fibroblasts and the ECM proteolytic degradation via matrix metalloproteinases (MMPs). Recent studies have demonstrated that in the diabetic heart, expression and activity of MMP-2 are reduced, resulting in increased collagen accumulation and cardiac dysfunction (2). These observations suggest that a MMP-related mechanism may contribute to cardiac fibrosis, and that it may be attenuated through stimulation of native MMP-2 expression or delivery of exogenous MMP-2. Therefore, reduced MMP-2 activity in DCM may represent a novel target for therapeutic treatment (3). To achieve this, a special proteolytically-stable delivery scaffold would be needed, because native ECM is rapidly degraded by MMPs. The goal of this study is to determine if self-assembling peptide nanofibers can be used for long-term (several weeks) MMP delivery and enhancement of cardiac remodeling. This study tests the hypothesis that increased MMP-2 concentration (native or exogenous) in the nanofiber environment will promote matrix remodeling in diabetic cardiac fibroblasts in vitro.

scholarly journals Long Non-Coding RNA 554 Promotes Cardiac Fibrosis via TGF-β1 Pathway in Mice Following Myocardial Infarction

2020 ◽  
Vol 11 ◽  
Author(s):  
Bihui Luo ◽  
Zhiyu He ◽  
Shijun Huang ◽  
Jinping Wang ◽  
Dunzheng Han ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Non Coding Rna ◽  
Novel Target ◽  
And Function ◽  
Tgf Β1

Rationale: Cardiac fibrosis is observed in nearly every form of myocardial disease. Long non-coding RNAs (lncRNAs) have been shown to play an important role in cardiac fibrosis, but the detailed molecular mechanism remains unknown.Object: We aimed at characterizing lncRNA 554 expression in murine cardiac fibroblasts (CFs) after myocardial infarction (MI) to identify CF-enriched lncRNA and investigate its function and contribution to cardiac fibrosis and function.Methods and Results: In this study, we identified lncRNA NONMMUT022554 (lncRNA 554) as a regulator of MI-induced cardiac fibrosis. We found that lncRNA 554 was significantly up-regulated in the mouse hearts following MI. Further study showed that lncRNA 554 was predominantly expressed in cardiac fibroblasts, indicating a potential role of lncRNA 554 in cardiac fibrosis. In vitro knockdown of lncRNA 554 by siRNA suppressed fibroblasts migration and expression of extracellular matrix (ECM); while overexpression of lncRNA 554 promoted expression of ECM genes. Consistently, lentivirus mediated in vivo knockdown of lncRNA 554 could inhibit cardiac fibrosis and improve cardiac function in mouse model of MI. More importantly, TGF-β1 inhibitor (TEW-7197) could reverse the pro-fibrotic function of lncRNA 554 in CFs. This suggests that the effects of lncRNA 554 on cardiac fibrosis is TGF-β1 dependent.Conclusion: Collectively, our study illustrated the role of lncRNA 554 in cardiac fibrosis, suggested that lncRNA 554 might be a novel target for cardiac fibrosis.

scholarly journals Up-Regulating Relaxin Expression by G-Quadruplex Interactive Ligand to Achieve Antifibrotic Action

Endocrinology ◽  
2012 ◽  
Vol 153 (8) ◽  
pp. 3692-3700 ◽  
Author(s):  
Hui-Ping Gu ◽  
Sen Lin ◽  
Ming Xu ◽  
Hai-Yi Yu ◽  
Xiao-Jun Du ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Heart Diseases ◽  
Gene Promoter ◽  
Binding Motif ◽  
Endogenous Expression ◽  
G Quadruplex

Myocardial fibrosis is a key pathological change in a variety of heart diseases contributing to the development of heart failure, arrhythmias, and sudden death. Recent studies have shown that relaxin prevents and reverses cardiac fibrosis. Endogenous expression of relaxin was elevated in the setting of heart disease; the extent of such up-regulation, however, is insufficient to exert compensatory actions, and the mechanism regulating relaxin expression is poorly defined. In the rat relaxin-1 (RLN1, Chr1) gene promoter region we found presence of repeated guanine (G)-rich sequences, which allowed formation and stabilization of G-quadruplexes with the addition of a G-quadruplex interactive ligand berberine. The G-rich sequences and the G-quadruplexes were localized adjacent to the binding motif of signal transducer and activator of transcription (STAT)3, which negatively regulates relaxin expression. Thus, we hypothesized that the formation and stabilization of G-quadruplexes by berberine could influence relaxin expression. We found that berberine-induced formation of G-quadruplexes did increase relaxin gene expression measured at mRNA and protein levels. Formation of G-quadruplexes significantly reduced STAT3 binding to the promoter of relaxin gene. This was associated with consequent increase in the binding of RNA polymerase II and STAT5a to relaxin gene promoter. In cardiac fibroblasts and rats treated with angiotensin II, berberine was found to suppress fibroblast activation, collagen synthesis, and extent of cardiac fibrosis through up-regulating relaxin. The antifibrotic action of berberine in vitro and in vivo was similar to that by exogenous relaxin. Our findings document a novel therapeutic strategy for fibrosis through up-regulating expression of endogenous relaxin.

Abstract 277: Microrna-33 Promotes Cardiac Fibrosis by Maintaining Cellular Lipid Homeostasis

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Masataka Nishiga ◽  
Takahiro Horie ◽  
Yasuhide Kuwabara ◽  
Osamu Baba ◽  
Tetsushi Nakao ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Pressure Overload ◽  
Cholesterol Content ◽  
Atp Binding Cassette Transporter ◽  
Primary Fibroblasts ◽  
Proliferation In Vitro ◽  
Altered Lipid

Background: A highly conserved microRNA, miR-33 is considered as a potential therapeutic target for atherosclerosis, because recent reports, including ours, indicated miR-33 has atherogenic effects by reducing HDL-C. However, the functions of miR-33 in heart failure remain to be elucidated. Methods and results: To clarify the functions of miR-33 involved in cardiac hypertrophy and fibrosis in vivo, we investigated the responses to pressure overload by transverse aortic constriction (TAC) in miR-33 deficient (KO) mice. When subjected to TAC, miR-33 expression level was significantly up-regulated in wild-type (WT) left ventricles, whereas miR-33 KO hearts displayed no less hypertrophic responses than WT hearts. However, interestingly, histological and gene expression analyses showed ameliorated cardiac fibrosis in miR-33 KO hearts compared to WT hearts. Furthermore, we generated cardiac fibroblast specific miR-33 deficient mice, which also showed ameliorated cardiac fibrosis when they were subjected to TAC. We also found that cardiac fibroblasts were mainly responsible for miR-33 expression in the heart, because its expression was about 4-folds higher in isolated primary cardiac fibroblasts than cardiomyocytes. Deficiency of miR-33 impaired cell proliferation in primary fibroblasts, which was considered due to altered lipid raft cholesterol content by up-regulated ATP-binding cassette transporter A1/G1. Conclusion: Deficiency of miR-33 impaired fibroblast proliferation in vitro, and ameliorated cardiac fibrosis induced by pressure overload in vivo.

Abstract 292: TRPA1 Promoting Myofibroblast Differentiation Mediate Pressure Overload-Induced Cardiac Fibrosis

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Shuang Li ◽  
Dong Han ◽  
Dachun Yang
Keyword(s):  
Knockout Mice ◽  
Molecular Mechanisms ◽  
Cardiac Fibrosis ◽  
Transient Receptor Potential ◽  
Transforming Growth Factor ◽  
Ventricular Remodeling ◽  
Cardiac Fibroblasts ◽  
Gene Transfection ◽  
Pressure Overload

Background: Hypertensive ventricular remodeling is a common cause of heart failure. Activation and accumulation of cardiac fibroblasts is the key contributors to this progression. Our previous studies indicate that transient receptor potential ankyrin 1 (TRPA1), a Ca 2+ channel necessary and sufficient, play a prominent role in ventricular remodeling. However, the molecular mechanisms regulating remain poorly understood. Methods: We used TRPA1 agonists cinnamaldehyde (CA) pretreatment and TRPA1 knockout mice to understand the role of TRPA1 in ventricular remodeling of hypertensive heart. We also examine the mechanisms through gene transfection and in vitro experiments. Results: TRPA1 overexpression fully activated myofibroblast transformation, while fibroblasts lacking TRPA1 were refractory to transforming growth factor β (TGF-β) -induced transdifferentiation. TRPA1 knockout mice showed hypertensive ventricular remodeling reversal following pressure overload. We found that the TGF-β induced TRPA1 expression through calcineurin-NFAT-Dyrk1A signaling pathway via the TRPA1 promoter. Once induced, TRPA1 activates the Ca 2+ -responsive protein phosphatase calcineurin, which itself induced myofibroblast transdifferentiation. Moreover, inhibition of calcineurin prevented TRPA1-dependent transdifferentiation. Conclusion: Our study provides the first evidence that TRPA1 regulation in cardiac fibroblasts transformation in response to hypertensive stimulation. The results suggesting a comprehensive pathway for myofibroblast formation in conjunction with TGF-β, Calcineurin, NFAT and Dyrk1A. Furthermore, these data indicate that negative modulation of cardiac fibroblast TRPA1 may represent a therapeutic strategy against hypertensive cardiac remodeling.

Abstract 782: Fra2 Mediates Oxygen-induced TGFbeta-1 mRNA Expression In Adult Cardiac Fibroblasts: Significance In Myocardial Fibrosis Following Ischemia-reperfusion Injury

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Sashwati Roy ◽  
Savita Khanna ◽  
Chandan K Sen
Keyword(s):  
Mrna Expression ◽  
Transforming Growth Factor Beta ◽  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Ischemia Reperfusion Injury ◽  
Cardiac Fibroblasts ◽  
Ischemia Reperfusion ◽  
Luciferase Reporter ◽  
Mrna Levels

Background . Transforming growth factor beta-1 (TGFbeta-1) is a key cytokine implicated in the development of cardiac fibrosis following ischemia-reperfusion (IR) injury. The profibrotic effects of TGFbeta-1 are primarily attributable to the differentiation of cardiac fibroblasts (CF) to myofibroblasts. Previously, we have reported perceived hyperoxia (Circ Res 92:264 –71), sub-lethal reoxygenation shock during IR, induces differentiation of CF to myofibroblasts at the infarct site. The mechanisms underlying oxygen-sensitive induction of TGFbeta-1 mRNA remain to be characterized. Hypothesis . Fra2 mediates oxygen-induced TGFbeta-1 mRNA expression in adult cardiac fibroblasts. Methods. TGFbeta-1 mRNA expression in infarct tissue was investigated in an IR injury model. The left anterior descending coronary artery of mice was transiently occluded for 60 minutes followed by reperfusion to induce IR injury. Spatially resolved infarct and non-infarct tissues were collected at 0, 1, 3, 5, and 7 days post-IR using laser capture microdissection. TGFbeta-1 mRNA levels were measured using real-time PCR. To investigate the role of oxygen in the regulation of TGFbeta-1, we used our previously reported model of perceived hyperoxia where CF (from 5wks old mice) after isolation were cultured at 5%O 2 (physiological pO 2 ) followed by transferring them to 20%O 2 to induce hyperoxic insult. Results & Conclusions. In vivo, a significant increase (p<0.01; n=5) in TGFbeta-1 mRNA was observed at the infarct site already at day 1 post-IR. The levels continued to increase until day 7 post-IR. In vitro, exposure of CF to 20%O 2 hyperoxic insult induced TGFbeta-1 mRNA (p<0.001; n=4) and protein (p<0.01; n=4) expression. Using a TGFbeta-1 promoter-luciferase reporter and DNA binding assays, we collected first evidence that AP-1 and its component Fra2 as major mediators of oxygen-induced TGFbeta-1 expression. Exposure to 20%O 2 resulted in increased localization of Fra2 in nucleus. siRNA-dependent Fra-2 knock-down completely abrogated oxygen-induced TGFbeta1 expression. In conclusion, this study presents first evidence that Fra-2 is involved in inducible TGFbeta1 expression in CF. Fra2 was noted as being central in regulating oxygen-induced TGFbeta-1 expression.s

Abstract 445: A Pro-Fibrotic Role of Interleukin-4 in Cardiac Remodeling and Dysfunction

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Hongmei Peng ◽  
Oscar Carretero ◽  
Xiao-Ping Yang ◽  
Pablo Nakagawa ◽  
Jiang Xu ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Interleukin 4 ◽  
Ang Ii ◽  
Collagen Production ◽  
And Function ◽  
First Time ◽  
Mini Pump

Elevated interleukin-4 (IL-4) levels are positively related to cardiac fibrosis in heart failure and hypertension. Using Balb/c exhibiting high circulating IL-4, Balb/c- Il4 tm2Nnt (IL-4 knockout with Balb/c background, IL-4 -/- ) and C57BL/6 mice, as well as cultured cardiac fibroblasts (CFs), we hypothesized that 1) high levels of IL-4 result in cardiac fibrosis, making the heart susceptible to angiotensin II (Ang II)-induced damage, and 2) IL-4 potently stimulates collagen production by CFs. Each strain (9- to 12-week old male) received vehicle or Ang II (1.4 mg/kg/day, s.c. via osmotic mini-pump) for 8 weeks. Cardiac fibrosis and function were determined by histology and echocardiography, respectively. Compared to C57BL/6, Balb/c mice had doubled interstitial collagen in the heart, enlarged left ventricle and decreased cardiac function along with elevated cardiac IL-4 protein (1.00±0.08 in C57BL/6 vs 2.61±0.46 in Balb/c, p <0.05); all those changes were significantly attenuated in IL-4 -/- (Table 1). Ang II further deteriorated cardiac fibrosis and dysfunction in Balb/c; these detrimental effects were attenuated in IL-4 -/- , although the three strains had a similar level of hypertension. In vitro study revealed that IL-4Rα was constitutively expressed in CFs (Western blot), and IL-4 potently stimulated collagen production by CFs (hydroxproline assay, from 18.89±0.85 to 38.81±3.61 μg/mg at 10 ng/ml, p <0.01). Our study demonstrates for the first time that IL-4, as a potent pro-fibrotic cytokine in the heart, contributes to cardiac fibrotic remodeling and dysfunction. Thus IL-4 may be a potential therapeutic target for cardiac fibrosis and dysfunction.

Abstract 313: Twist Contributes to Cardiomyocyte Renewal and is Required for Maintenance of Adult Cardiac Function

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Yi-Li Min ◽  
Svetlana Bezprozvannaya ◽  
Drazen Šošic ◽  
Young-Jae Nam ◽  
Hesham Sadek ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Cardiac Fibroblasts ◽  
Cell Lineage ◽  
Cardiac Regeneration ◽  
Cell Types ◽  
Bhlh Transcription Factor ◽  
Adult Heart ◽  
Twist 1 ◽  
Essential Contribution

Cardiomyocyte renewal occurs very slowly in adult mammals, and little is known of the genetic basis of cardiac regeneration. Twist is a highly conserved bHLH transcription factor responsible for Drosophila mesoderm formation during embryogenesis. Recent studies have shown that Twist protein is essential for muscle regeneration in adult Drosophila, but the potential role of Twist in the mammalian heart has not been explored. There are two Twist genes in vertebrates, Twist-1 and -2. We show that Twist-1 and -2 are expressed in epicardium and interstitial cells but not in differentiated cardiomyocytes in mice. To understand the potential function of Twist-dependent lineages in the adult heart, we generated inducible Twist2CreERT2; ROSA26-tdTomato reporter mice. By treating these mice with tamoxifen at 8 weeks of age, we observed progressive labeling of various cell types, such as epithelial cells, cardiac fibroblasts, and cardiomyocytes in the heart. We isolated Tomato-positive nonmyocytes from these mice and found that these cells can differentiate into cardiomyocytes and other cell types in vitro. Furthermore, cardiac-specific deletion of both Twist1 and Twist2 resulted in an age-dependent lethal cardiomyopathy. These findings reveal an essential contribution of Twist to long-term maintenance of cardiac function and support the concept of slow, lifelong renewal of cardiomyocytes from a Twist-dependent cell lineage in the adult heart.

scholarly journals Effects of Sex and 17 β-Estradiol on Cardiac Fibroblast Morphology and Signaling Activities In Vitro

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2564
Author(s):  
Kelsey Watts ◽  
William J. Richardson
Keyword(s):  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Cellular Level ◽  
Cellular Morphology ◽  
Structural Level ◽  
Experimental Conditions ◽  
Male And Female ◽  
Protein Protein Interaction ◽  
Complex Signaling

Several studies have demonstrated estrogen’s cardioprotective abilities in decreasing the fibrotic response of cardiac fibroblasts (CFs). However, the majority of these studies are not sex-specific, and those at the cellular level utilize tissue culture plastic, a substrate with a much higher stiffness than physiological conditions. Understanding the intrinsic differences between male and female CFs under more physiologically “healthy” conditions will help to elucidate the divergences in their complex signaling networks. We aimed to do this by conducting a sex-disaggregated analysis of changes in cellular morphology and relative levels of profibrotic signaling proteins in CFs cultured on 8 kPa stiffness plates with and without 17 β-estradiol (E2). Cyclic immunofluorescent analysis indicated that there was a negligible change in cellular morphology due to sex and E2 treatment and that the differences between male and female CFs occur at a biochemical rather than structural level. Several proteins corresponding to profibrotic activity had various sex-specific responses with and without E2 treatment. Single-cell correlation analysis exhibited varied protein–protein interaction across experimental conditions. These findings demonstrate the need for further research into the dimorphisms of male and female CFs to develop better tailored sex-informed prevention and treatment interventions of cardiac fibrosis.

Abstract 866: Secreted Frizzled Related Protein 2 Modulates Post Myocardial Infarct Remodeling by Inhibiting Collagen Maturation through the Inhibition of Bone Morphogenetic Protein 1 Activity

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Wei He ◽  
Lunan Zhang ◽  
Richard E Pratt ◽  
Victor J Dzau
Keyword(s):  
Myocardial Infarction ◽  
Molecular Mechanisms ◽  
Cardiac Fibrosis ◽  
Myocardial Infarct ◽  
Primary Cultures ◽  
The United States ◽  
Coronary Artery Ligation ◽  
Related Protein ◽  
Artery Ligation

Myocardial infarction and post-infarction remodeling with heart failure are the major cause of mortality and morbidity in the United States. We recently reported that intracardiac implantation of genetically engineered mesenchymal stem cell (MSC) overexpressing the Akt gene dramatically reduced the infarct size and restored cardiac functions in rodent hearts after coronary artery ligation. Further, we identified Secreted Frizzled Related Protein 2 (sfrp2) as a key factor released by Akt-MSC mediating myocardial survival and repair. However, the underlying mechanism remains elusive. Bone Morphogenetic Protein1 (BMP1)/Tolloid (TLD)-like metalloproteinases belong to a subgroup of astacin family and play key roles in the regulation of extracelluar matrix (ECM) formation and cardiac fibrosis. These proteases have procollagen C-proteinase (PCP) activities which are responsible for the cleavage of C-propeptides from procollagen precursors to produce mature collagen fibrils. In this report, we showed that three days following myocardial infarction in rats, both BMP1 protein expression and activity were upregulated in the infarcted left ventricle. Interestingly, we found recombinant sfrp2 could inhibit BMP1 activity in MI tissue samples as measured by an in vitro PCP activity assay. Furthermore, using purified recombinant proteins, we demonstrated that sfrp2, but not sfrp1 or sfrp3, inhibited BMP-1 activity in vitro. Moreover, purified sfrp2 could physically interact with BMP1 protein as shown by the co-immunoprecipitation assay. To provide further evidence that sfrp2 can interfere with collagen processing, we demonstrated that exogenously added sfrp2 interfered with procollagen processing in primary cultures of cardiac fibroblast culture medium. Similar results were obtained when these cells were transiently transfected with sfrp2 expressing plasmids. In summary, our data suggest that one of the molecular mechanisms underlying the cardioprotective and repair effects of sfrp2 protein on myocardial infarction is through the inhibition of BMP-1 activity. Therefore, sfrp2 has the potential clinical application as a novel anti-fibrotic reagent for the modulation of cardiac remodeling after acute myocardial infarction.

Abstract 18698: Identification of a Novel Cardiac Progenitor Population Expressing Pw1/peg3 in the Murine Heart

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Elisa Yaniz-Galende ◽  
Luigi Formicola ◽  
Nathalie Mougenot ◽  
Lise Legrand ◽  
Jiqiu Chen ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Fold Increase ◽  
Cardiac Regeneration ◽  
Cardiac Repair ◽  
Cardiac Progenitor Cells ◽  
Average Percentage ◽  
Pathological Conditions ◽  
Reporter Mice ◽  
Novel Target

The myocardium responds to injury by recruiting cardiac progenitor cells (CPCs) to the injured tissue to promote cardiac repair. Although different classes of CPCs have been identified, their contribution in physiological and pathological conditions remains unclear. PW1 gene has recently been proposed as a marker of resident adult stem and progenitor cell populations in several adult tissues. Our goal was to characterize and determine the role of PW1+ population in the heart. Here, we employ immunostaining and fluorescence-activated cell sorting (FACS) analysis in PW1-reporter mouse to perform qualitative and quantitative analyses of PW1+ population in the heart. We first found that PW1+ cells are mainly located in the epicardium and myocardial interstitium of normal hearts. The average percentage of PW1+ cells, as assessed by FACS, was 1.56±1.41%. A subset of PW1+ cells also co-express other CPC markers such as Sca-1 (52±22%) or PDGFR1α (43±14%). In contrast, a very small proportion of PW1+ cells co-express c-kit (6±5%). To investigate the contribution of PW1+ cells in pathological conditions, we then performed myocardial infarction (MI) by LAD ligation in PW1-reporter mice. We found that MI resulted in a 3-fold increase in the number of PW1+ cells in infarcted mice compared with sham-operated groups, at 1 week post-MI (1.16%±0.47% in sham versus 3.43%±0.82 in MI). This population preferentially localized in the injured myocardium and border area. PW1+ cells were isolated by FACS from the whole infarcted heart from PW1-reporter mice. In vitro differentiation assays reveal that purified PW1+ cells are multipotent and can spontaneously differentiate into smooth muscle cells, endothelial cells and cardiomyocyte-like cells. Taken together, our data identify a novel PW1+ cardiac progenitor population with the potential to undergo differentiation into multiple cardiac lineages, suggesting their involvement in cardiac repair in normal and pathological conditions. The discovery of a novel population of cardiac progenitor cells, augmented following MI and with cardiogenic potential, provides a novel target for therapeutic approaches aimed at improving cardiac regeneration.

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