Home is where the heart is: via the FROUNT

In this issue of Cell Stem Cell, Belema-Bedada et al. (2008) describe a novel mechanism by which bone marrow-derived adult mesenchymal stem cells migrate to sites of damaged heart tissue. This process is dependent on the intracellular adaptor molecule FROUNT, which interacts with the chemokine receptor CCR2.     

Getting to the heart of COX-2 inhibition

Aspirin protects against heart disease, while COX-2 Inhibitors appear to injure the heart. The studies by [this Issue of Cell Metabolism]) shed light on two distinct prostaglandin receptors contributing to these conflicting cardiovascular effects.     

Are Hematopoietic Stem Cells Generated in the Placenta?

In this issue of Cell Stem Cell, the origin of multipotent hematopoietic cells present in the placenta has been assessed in Ncx1(-/-) embryos lacking a functional heart and circulation. Rhodes and colleagues (Rhodes et al., 2008) found lymphoid progenitors in the placenta, as well as in dorsal aorta and yolk sac and vitelline vessels, indicating that they arose in situ.     

Rewind to recover: dedifferentiation after cardiac injury

In adult mammals, cardiomyocytes are known to reactivate an embryonic gene-expression program after injury. In this issue of Cell Stem Cell, Kubin et al. (2011) show that oncostatin M regulates this dedifferentiation which, while beneficial for recovery from acute injury, if persistent results in heart failure in both rodents and humans.     

A repair "kit" for the infarcted heart

Transplanted, c-kit expressing marrow-derived progenitors can enhance the function of an infarcted heart, but the mechanism remains unclear. In this issue of Cell Stem Cell, Loffredo et?al. (2011) provide evidence that hematopoietic precursors do not differentiate into new cardiomyocytes but, rather, stimulate production of new cardiomyocytes from endogenous progenitors.     

The HeArt of regeneration

Fish and amphibian hearts are known to regenerate after partial resection, but the molecular mechanisms underlying this process remain unclear. In this issue of Cell, Lipilina et al. analyze regeneration in the zebrafish heart. Their work indicates that new cardiomyocytes originate from undifferentiated progenitor cells and reveals a critical role for the epicardium, the cellular layer that covers the heart.     

Hope for a broken heart?

Heated debate has surrounded the issue of whether adult stem cells can differentiate into cardiac myocytes and contribute to the function of the heart. In this issue of Cell, demonstrate stem cells in the adult rat heart that differentiate into cardiac myocytes in vitro and, when injected into the adult rat heart, can reconstitute the injured myocardium and improve function. These findings should weigh heavily in future debates about the existence of stem cells in the adult heart and their capacity for functional repair after injury.     

Characterization of N-cadherin mRNA in chicken brain and heart by means of oligonucleotide probes

It has previously been reported, that there is only one mRNA of 4.3 kb for chicken N-cadherin in brain and heart and one gene [(1988) J. Cell Biol. 106, 873-881]. Using three synthetic oligonucleotide probes derived from the published chicken N-cadherin cDNA sequence we found hybridization to at least four mRNAs in chicken brain and heart. The measured sizes were 8.0, 4.7, 3.8, and 3.3 kb. The 8.0 kb mRNA is only seen in brain, and only when a cytoplasmic probe is employed. The 3.8 kb mRNA is only observed in heart.     

Apelin and its g protein-coupled receptor regulate cardiac development as well as cardiac function

The Apelin pathway has only recently emerged as an important regulator of cardiac and vascular function, mediating adaptation to physiological stress and disease. In this issue of Developmental Cell, experiments in zebrafish convincingly show a critical role for this pathway in myocardial cell specification and heart development.     

The first "Slit" is the deepest: the secret to a hollow heart

Tubular organs are essential for life, but lumen formation in nonepithelial tissues such as the vascular system or heart is poorly understood. Two studies in this issue (Medioni, C., M. Astier, M. Zmojdzian, K. Jagla, and M. Sémériva. 2008. J. Cell Biol. 182:249-261; Santiago-Martínez, E., N.H. Soplop, R. Patel, and S.G. Kramer. 2008. J. Cell Biol. 182:241-248) reveal unexpected roles for the Slit-Robo signaling system during Drosophila melanogaster heart morphogenesis. In cardioblasts, Slit and Robo modulate the cell shape changes and domains of E-cadherin-based adhesion that drive lumen formation. Furthermore, in contrast to the well-known paracrine role of Slit and Robo in guiding cell migrations, here Slit and Robo may act by autocrine signaling. In addition, the two groups demonstrate that heart lumen formation is even more distinct from typical epithelial tubulogenesis mechanisms because the heart lumen is bounded by membrane surfaces that have basal rather than apical attributes. As the D. melanogaster cardioblasts are thought to have significant evolutionary similarity to vertebrate endothelial and cardiac lineages, these findings are likely to provide insights into mechanisms of vertebrate heart and vascular morphogenesis.     

Overexpression of elastin fragments in infarcted myocardium attenuates scar expansion and heart dysfunction

Ventricular dilation after myocardial infarction can cause heart failure. Increasing strength and elasticity in the infarct region might prevent ventricular dilation. Because elastin provides strength, extensibility, and resilience to tissues and maintains tissue architecture, we studied the effect of elastin expression in the infarct on scar expansion and heart function. COS-7 cells transfected with a plasmid with an elastin gene fragment or a vector were seeded into a Gelfoam mesh and cultured. Mechanical stretch test (n = 5/group) showed that the elastin mesh was more elastic (P < 0.05) and tensile (P < 0.05) than the vector mesh. In an in vivo study in rats, 6 days after left anterior descending coronary artery ligation, COS-7 cells (Cell group, n = 7) or COS-7 cells with elastin gene (Elastin group, n = 9) or vector (Vector group, n = 9) were transplanted into the infarct; infarcted rats served as controls (n = 7). Over 8 wk the Cell group did not demonstrate effects on scar expansion and deterioration of heart function vs. controls. In contrast, infarct expansion was smaller and heart function was better maintained in the Elastin group vs. the Vector group (P < 0.05). At 8 wk after cell transplantation Langendorff data showed that the Elastin group had greater (P < 0.01) developed pressure and a smaller left ventricular volume than the Vector group. Western blot and histology showed accumulated elastin in the Elastin group infarct. Changing the extracellular matrix composition of a myocardial infarct by increasing elastin fragment content attenuated scar expansion, ventricular dilation, and onset of heart dysfunction.     

心血管发育中的分子调控及其相关疾病

在心脏发育中,心血管的发育至关重要,其中细胞增殖参与调控心脏的正常发育.细胞增殖是通过细胞周期而实现的.在细胞周期中,细胞周期调控分子(包括细胞周期蛋白,依赖于细胞周期蛋白的蛋白激酶及其抑制因子)和信号通道(包括丝裂激活蛋白、内皮素-1等)的调控表达的改变导致整个心血管系统的重塑,并常伴随着心血管系统的紊乱,引起如心肌梗塞、心肌炎、及充血性心力衰竭等相关疾病.     

CaMKII: new tricks for an old dog

Calcium/calmodulin-dependent protein kinase II (CaMKII) is a pivotal signaling molecule in both the brain and the heart. In this issue of Cell, Erickson et al. (2008) demonstrate a mechanism for CaMKII activation by reactive oxygen species that provides a direct link between kinase activation and cardiac dysfunction.     

Energizer: PGC-1 alpha keeps the heart going

In the current issue of Cell Metabolism, Arany et al. (2005) demonstrate essential roles for PGC-1alpha in cardiac metabolism, proving several long-postulated functions while disproving others. These experiments conclusively reinforce the logic of rescuing PGC-1alpha as a novel therapeutic target in heart failure.     

Coordinating morphogenesis: epithelial integrity during heart tube assembly

Formation of the embryonic heart tube requires the medial migration and merger of bilateral precursor populations. A new study of zebrafish cardiogenesis published in this issue of Developmental Cell indicates that precursor migration involves formation of a coherent epithelium and that fibronectin plays an important role in maintaining cardiac epithelial integrity.     

STAT蛋白在心脏疾病中作用的研究进展

细胞信号转导途径JAK-STAT通路是细胞因子由细胞膜外向细胞核内传递信号的主要途径,参与了介导细胞生长,增殖分化,炎症反应,细胞凋亡等多种病理生理过程。STAT蛋白是JAK-STAT通路的核心分子,且所有的STAT蛋白在心脏中均有表达,改变其分子结构能调节STAT蛋白的生物学活性。目前,已有大量文献报道了STAT1、STAT3在心脏疾病中的作用,缺血性心脏疾病、缺血再灌注引起心肌损伤、心肌肥大、心肌梗塞后的心脏衰竭以及缺血预/后处理介导的心脏保护作用等均与STAT蛋白密切相关。本文主要就近年来STAT蛋白在心脏疾病中作用的研究进展进行了综述。     

Marsupial cells in long-term culture

Cell lines have been developed from several species of Australian marsupials and studied during long-term growth. Cell lines developed from macropodid skin or heart tissues all had reproducible finite life-spans. However, cell lines developed from dasyurids showed bariable behavior in culture: lines developed from Antechinus stuartii and Dasyurus viverrinus had finite life-spans, while lines developed from Sminthopsis crassicaudata had indefinite life-spans. S. crassicaudata lines usually became heteroplloid, but one was still diploid after 150 population doublings, while another contained a proportion (10%) of haploid cells. Other lines were developed from the peramelid, Perameles nasuta, and the phanlngerid, Trichosurus vulpecula.     

Cellularity of organs in mature rams of different breeds

The relative importance of cell number and cell size in determining the mass of 16 organs and tissues in mature rams of six different breeds was studied through estimation of organ deoxyribonucleic acid (DNA) content. The mean fleece-free empty body weight (FFEBW) ranged from 54.6 +/- 0.3 kg for Camden Park Merinos to 76.7 +/- 1.6 kg for Strong Wool Merinos. For all organs, mass increased with FFEBW, but the relationship was significant across all sheep for only eight organs (blood, kidney, liver, abomasum, vastus lateralis muscle, skin, perirenal fat and triceps muscle). There were significant differences between breeds in the mass of 11 organs. With four (heart, rumen reticulum, small intestine and testicular fat) this difference was independent of breed differences in FFEBW, whereas with another four (kidney, abomasum, vastus lateralis muscle and skin), it was closely related to FFEBW. Breed differences in the mass of the remaining three organs (blood, liver and perirenal fat) were partly related to FFEBW and partly breed specific. Blood mass increased with FFEBW across all animals, but, within a breed, it declined as FFEBW increased. The increase in the mass of perirenal fat with FFEBW was significantly greater within a breed than between breeds. Cell number increased significantly with the mass of all organs except blood and brain. There were between-breed differences in the number of cells in seven organs (liver, heart, rumen reticulum, abomasum, small intestine, vastus lateralis muscle and skin), which, except for heart, were attributable to between-breed differences in organ mass. With heart, the increase in cell number with organ mass within a breed was greater than across all breeds. Cell size was significantly related to organ mass only with vastus lateralis muscle, spleen, perirenal fat and liver. The relationship for vastus lateralis muscle and spleen was negative, indicating that cells were smaller in larger organs. There were differences between breeds in cell size for heart, vastus lateralis and triceps muscles. These differences for heart and triceps muscle were breed specific, whereas for vastus lateralis muscle it was attributed to breed differences in organ weight. There was a 30-fold range in mean cell size across organs, with adipose tissue having the largest cells, muscle tissue intermediate and visceral tissues the smallest. In general, organ mass is positively related to FFEBW. Cell number, not cell size, is largely responsible for differences in organ mass between mature sheep of different breeds.     

Insulin induces changes in the subcellular distribution of actin and 5′-nucleotidase

The present study utilized a cultured adult myocardial cell model to examine the arachidonic acid metabolism under different cell-damaging and normoxic conditions. Cell injury was caused by short-time hypoxia, calcium ionophore A 23187-triggered cell-damage under hypoxia and cell disruption by freezing and thawing. The current study demonstrates that under the cell-damaging conditions cultured adult heart myocytes resemble myocardial cells under normoxic conditions in metabolizing arachidonic acid into triacylglycerols and phospholipids as the major route (a), in formation of ETYA-inhibitable indomethacin-resistant lipid metabolites in minor amounts (b) and in being independent of calcium overload in the metabolic pathways of arachidonic acid metabolism (c). The ETYA-inhibitable components were resolved by HPLC. There was no evidence in formation of lipoxygenase products. The results were supported by negative hybridisation experiments of the total mRNA isolated from adult myocardial cells with a cDNA probe of a red-cell-specific lipoxygenase mRNA. We conclude from these observations that cell injury does not result in expression of lipoxygenase activities in heart myocytes.Abbreviations HETE Hydroxyeicosatetraenoic acid - DiHETE Dihydroxyeicosatetraenoic acid - ETYA 5.8.11.14-Eicosatetraynoic acid - TLC Thin-Layer Chromatography - NP-HPLC Normal Phase-High Performance Liquid Chromatography - RBC Red Blood Cell - LOX Lipoxygenase     

Expression of a novel tropomyosin isoform in axolotl heart and skeletal muscle

TPM1κ is an alternatively spliced isoform of the TPM1 gene whose specific role in cardiac development and disease is yet to be elucidated. Although mRNA studies have shown TPM1κ expression in axolotl heart and skeletal muscle, it has not been quantified. Also the presence of TPM1κ protein in axolotl heart and skeletal muscle has not been demonstrated. In this study, we quantified TPM1κ mRNA expression in axolotl heart and skeletal muscle. Using a newly developed TPM1κ specific antibody, we demonstrated the expression and incorporation of TPM1κ protein in myofibrils of axolotl heart and skeletal muscle. The results support the potential role of TPM1κ in myofibrillogenesis and sarcomeric function. J. Cell. Biochem. 110: 875–881, 2010. © 2010 Wiley‐Liss, Inc.