Notch signaling is vital for proper cardiovascular development and function in both humans and animal models. Indeed, mutations in either JAGGED or NOTCH cause congenital heart disease in humans and NOTCH mutations are associated with adult valvular disease. Notch typically functions to mediate developmental interactions between adjacent tissues. Here we ...

AIMS: Cells derived from the stroma vascular fraction (SVF) of mouse adipose tissue can spontaneously give rise to rare, functional, cardiac-like cells in vitro. This study aimed to improve the production of adipose-derived cardiomyogenic cells (AD-CMG), to characterize them and to assess their cardiac fate and functional outcomes after their ...

The GATA transcription factor encoded by pannier (pnr) is a critical regulator of heart progenitor formation in Drosophila. Mutations in GATA4, the mammalian homolog of pnr, have also been implicated in causing human cardiac disease in a haploinsufficient manner. Mouse models of Gata4 loss-of-function and gain-of-function studies underscored the importance ...

Here we show the temporal-spatial orchestration of early heart morphogenesis at cellular level resolution, in vivo, and reconcile conflicting positional fate mapping data regarding the primary heart-forming field(s). We determined the positional fates of precardiac cells using a precision electroporation approach in combination with wide-field time-lapse microscopy in the quail ...

Transplantation of human embryonic stem cell-derived cardiomyocytes (hESC-CM) has been shown to improve the function of the rodent heart 1 month after myocardial infarction (MI). However, the mechanistic basis and optimal delivery strategies are unclear. We investigated the influence of the number of injected cells, resulting graft size, and possible ...

During acute myocardial infarction (AMI), ischemia leads to necrotic areas surrounded by border zones of reversibly damaged cardiomyocytes, showing membrane flip-flop. During reperfusion type IIA secretory phopholipase A(2) (sPLA(2)-IIA) induces direct cell-toxicity and facilitates binding of other inflammatory mediators on these cardiomyocytes. Therefore, we hypothesized that the specific sPLA(2)-IIA-inhibitor PX-18 ...

In a first paper, we concluded that the muscular region of the interventricular septum is developed by the trabecular branches and showed evidence that the developing interventricular septum elongates in a direction opposite to that of atria. Nevertheless, to date the literature is lacking precise information on the importance of ...

Aberrant transcriptional regulation contributes to the pathogenesis of both congenital and adult forms of heart disease. While the transcriptional regulator friend of Gata 2 (FOG2) is known to be essential for heart morphogenesis and coronary development, its tissue-specific function has not been previously investigated. Additionally, little is known about the ...

Cardiac performance after myocardial infarction is compromised by ventricular remodeling, which represents a major cause of late infarct-related chronic heart failure and death. In recent years, the scientists' interest has focused on the hypothesis that the administration of bone marrow progenitors, following myocardial infarction, could ameliorate left ventricular remodeling by ...

BACKGROUND: Cardiomyocyte apoptosis takes place at an early stage after myocardial infarction (MI). Therapy with mesenchymal stem cells (MSCs) is reported to reduce apoptosis. OBJECTIVES: To determine whether anoxic preconditioning (AP) could enhance the antiapoptotic effect of MSCs. METHODS: Cultured cardiomyocytes were treated with Dulbecco's modified Eagle's medium (as a ...

Transcoronary transplantation of progenitor cells has been proposed as a novel therapy for ischemic heart failure. The primary aims were to assess the feasibility of obtaining CD34+ cells from blood without mobilization in chronic conditions and to compare homing with results reported in acute conditions. We also evaluated the effect ...

Cell transplantation is an emerging therapy for treating post-infarction heart failure. Although the paracrine effect has been proposed to be an important mechanism for the therapeutic benefits, details remain largely unknown. This study compared various aspects of the paracrine effect after transplantation of either bone marrow mononuclear cells (BMC) or ...

The goal of this investigation was to determine the distribution of myocardial apoptosis in myocytes and nonmyocytes in primates and patients with heart failure (HF). Almost all clinical cardiologists and cardiovascular investigators believe that myocyte apoptosis is considered to be a cardinal sign of HF and a major factor in ...

AIMS: Our objective was to test whether progenitor cell proliferation and differentiation potential may vary depending upon the disease of the donor. METHODS AND RESULTS: Human cardiac mesoangioblasts were isolated from cardiac muscle biopsies of patients undergoing open heart surgery for correction of mitral regurgitation following an acute myocardial infarction ...

Heart mitochondria, which, depending on their location within cardiomyofibers, are classified as either subsarcolemmal or interfibrillar, are the major sources of the high energy compound, adenosine triphosphate. Physiological differences between these two populations are reflected by differences in the morphology of their cristae, with those of subsarcolemmal mitochondria being mostly ...

The aim of this study was to investigate the effect of intracoronary administration of freshly isolated, uncultured autologous tissue-derived stromal cells on cardiac function and perfusion after acute infarction in pigs. A transmural myocardial infarction in a porcine model was induced by occlusion of the mid LAD with an angioplasty ...

The primary myocardium of the embryonic heart, including the atrioventricular canal and outflow tract, is essential for septation and valve formation. In the chamber-forming heart, the expression of the T-box transcription factor Tbx2 is restricted to the primary myocardium. To gain insight into the cellular contributions of the Tbx2+ primary ...

Cellular transplantation represents a promising therapy for myocardial infarction (MI). However, it is limited by low transplanted cell retention and survival within the ischemic tissue. This study was designed to investigate whether injectable alpha-cyclodextrin/poly(ethylene glycol)-b-polycaprolactone-(dodecanedioic acid)-polycaprolactone-poly(ethylene glycol) (MPEG-PCL-MPEG) hydrogel could improve cell transplant retention and survival, reduce infarct expansion and ...

Myocardial infarction results in loss of cardiomyocytes, scar formation, ventricular remodelling, and eventually heart failure. In recent years, cell therapy has emerged as a potential new strategy for patients with ischaemic heart disease. This includes embryonic and bone marrow derived stem cells. Recent clinical studies showed ostensibly conflicting results of ...

Fibroblast growth factor receptor (FGFR) is expressed in a variety of cells and is involved in their proliferation/migration/survival. To elucidate FGFR-mediated specific action of vascular endothelial cells (ECs) on myocardial ischemia, we generated endothelium-targeted transgenic mice overexpressing constitutively active FGFR2 using Tie2 promoter (FGFR2-Tg). Infarct size, vessel formation and blood ...

Differentiation of foetal cardiomyocytes is accompanied by sequential actin isoform expression, i.e. down-regulation of the 'embryonic' alpha smooth muscle actin, followed by an up-regulation of alpha skeletal actin (alphaSKA) and a final predominant expression of alpha cardiac actin (alphaCA). Our objective was to detect whether re-expression of alphaSKA occurred during ...

AIM: A limitation of cell therapy for heart disease is the fact that stem cells injected directly into the myocardium are capable of entering the vasculature and migrating to remote organs. We determined whether retention of mesenchymal stem cells (MSCs) in the infarcted myocardium could be improved by implanting the ...

Amongst animal species, there is enormous variation in the size and complexity of the heart, ranging from the simple one-chambered heart of Ciona intestinalis to the complex four-chambered heart of lunged animals. To address possible mechanisms for the evolutionary adaptation of heart size, we studied how growth of the simple ...

We compared therapeutic benefits of intramyocardial injection of unfractionated bone marrow cells (BMCs) versus BMC extract as treatments for myocardial infarction (MI), using closed-chest ultrasound-guided injection at a clinically relevant time post-MI. MI was induced in mice and the animals treated at day 3 with either: (i) BMCs from green ...

BACKGROUND: Therapeutic ultrasound-mediated microbubble destruction has been applied in the targeted delivery of genes, drugs and stem cells. We intended to study whether diagnostic US irradiating lipid-coated microbubble destruction combined with bone-marrow derived MSC infusion could enable the targeted delivery of MSCs into the myocardium and improve cardiac function of ...

A major limitation to the application of stem-cell therapy to repair ischemic heart damage is the low survival of transplanted cells in the heart, possibly due to poor oxygenation. We hypothesized that hyperbaric oxygenation (HBO) can be used as an adjuvant treatment to augment stem-cell therapy. Therefore, the goal of ...

Uncovering the origins of myocardial cells is important for understanding and treating heart diseases. Cai et al. suggest that Tbx18-expressing epicardium provides a substantial contribution to myocytes in the ventricular septum and the atrial and ventricular walls. Here we show that the T-box transcription factor gene 18 (Tbx18) itself is ...

BACKGROUND: Acute myocardial infarction (AMI) is followed by post AMI cardiac remodelling, often leading to congestive heart failure. Homing of c-kit+ endothelial progenitor cells (EPC) has been thought to be the optimal source for regenerating infarcted myocardium. METHODS: Immune function of viable peripheral blood mononuclear cells (PBMC) was evaluated after ...

OBJECTIVE: Various patch materials currently used for cardiac reconstruction represent non-viable tissue with high susceptibility to infection and degeneration. We therefore introduce an innovative, autologous vascularized matrix with high regenerative potential for myocardial reconstruction. METHODS: Autologous small bowel segments without mucosa, but with both the adjacent jejunal artery and vein, ...

The mineralocorticoid pathway is involved in cardiac arrhythmias associated with heart failure through mechanisms that are incompletely understood. Defective regulation of the cardiac ryanodine receptor (RyR) is an important cause of the initiation of arrhythmias. Here, we examined whether the aldosterone pathway might modulate RyR function. Using the whole-cell patch ...

The proepicardium (PE) is a transient structure that forms at the venous pole of the embryonic vertebrate heart. This cardiac progenitor cell population gives rise to the epicardium, coronary vasculature, and fibroblasts. In the chicken embryo, the PE displays left-right (L-R) asymmetry and develops only on the right side, while ...

In this study we investigated cardiomyocyte differentiation of rat bone marrow-mesenchymal stem cells (BM-MSCs) by treating the stem cells with conditions mimicking that of myocardial infarction. The extract from infarcted rat myocardium contained the biochemical factors arising after infarction. The cardiac contraction and relaxation were simulated by applying 4% strain ...

Expression of cardiac ankyrin repeat protein (CARP) is augmented in heart failure due to dilated or ischaemic cardiomyopathy. It is unclear whether CARP is upregulated in heart failure due to arrhythmogenic right ventricular cardiomyopathy (ARVC). In the present study, we investigated the expression pattern of CARP and the correlation between ...

BACKGROUND: Until now, cell therapy has constituted a passive therapeutic approach; the only effects seem to be related to the reduction of the myocardial fibrosis and the limitation of the adverse ventricular remodeling. Cardiac resynchronization therapy is indicated in patients with heart failure to correct conduction disorders associated with chronic ...

We investigated pharmacological effects of rutin isolated form Lonicera japonica on H2O2-induced cell death in H9c2 cells in vitro and rat myocardial ischemia-reperfusion injury model in vivo. Western blot analysis showed that H2O2 increased expression of cleaved form of caspase-3 and proapoptotic Bax protein, but decreased antiapoptotic Bcl-2 protein in ...

Congenital heart diseases (CHD) result from abnormal morphogenesis of the embryonic cardiovascular system and usually involve defects in specific structural components of the developing heart and vessels. Therefore, an understanding of "Molecular Embryology", with specific focus on the individual modular steps involved in cardiovascular morphogenesis, is particularly relevant to those ...

In this issue of Cell Stem Cell, Zaruba et al. (2009) describe a pharmacoregenerative strategy for myocardial infarction. Using G-CSF to release progenitors from bone marrow and protease inhibition to prevent degradation of the homing signal, SDF-1, the authors achieve increased recruitment to the heart and improved heart function.

Ischemic cardiomyopathy is one of the main causes of death, which may be prevented by stem cell-based therapies. SDF-1alpha is the major chemokine attracting stem cells to the heart. Since SDF-1alpha is cleaved and inactivated by CD26/dipeptidylpeptidase IV (DPP-IV), we established a therapeutic concept--applicable to ischemic disorders in general--by combining ...

T-tubular invaginations of the sarcolemma of ventricular cardiomyocytes contain junctional structures functionally coupling L-type calcium channels to the sarcoplasmic reticulum calcium-release channels (the ryanodine receptors), and therefore their configuration controls the gain of calcium-induced calcium release (CICR). Studies primarily in rodent myocardium have shown the importance of T-tubular structures for ...

Reperfusion therapy has significantly improved survival and prognosis of patients with acute myocardial infarction. However, the development of heart failure, particularly in patients after a large myocardial damage, remains a major challenge. Cell therapy may provide a novel therapeutic option to modify left ventricular remodeling processes and prevent post-infarction heart ...

Comprehensive management of patients with chronic ischemic disease is a critically important component of clinical practice. Cardiac myocytes have the potential to adapt to limited flow conditions by adjusting contractile function, reducing metabolism, conserving resources, and preserving myocardial integrity to cope with an oxygen and (or) nutrition shortage. A prime ...

As a hallmark of heart disease, cardiac fibrosis contributes to the development of heart failure and arrhythmias and forms a key therapeutic target. There is a major unmet need for selective, potent, and safe antifibrotic drugs. Earlier studies revealed a cardiac fibrosis phenotype in relaxin-1-deficient mice. Recent studies in several ...

A well-circumscribed, expansile, and nonencapsulated cardiac rhabdomyoma composed of tightly arranged, large, variably sized, ovoid to irregular, swollen myocytes with deeply eosinophilic cytoplasm and varying degrees of cytoplasmic vacuolation was detected in an eight- to nine-month-old female beagle dog in a routine toxicology study. By histochemistry, the neoplasm was periodic ...

BACKGROUND: Animal studies have suggested dramatic improvement in cardiac function after acute myocardial infarction (AMI) through regeneration of the myocardium or neovascularization by transfer of cells derived from bone marrow (BMC) generated clinical studies. Recently published small sized studies have yielded mixed results, leaving the question unanswered. HYPOTHESIS: We analyzed ...

Recent animal studies and clinical trials have reported the scope of heart-resident ckit-positive stem cells in regenerating infarcted myocardium. The determinants of successful isolation of such cells are unknown. The objective of this study was to determine the influence of risk factors for coronary artery disease and disease severity on ...

Administration of mesenchymal stem cells (MSCs) is an effective therapy to repair cardiac damage after myocardial infarction (MI) in experimental models. However, the mechanisms of action still need to be elucidated. Our group has recently suggested that MSCs mediate their therapeutic effects primarily via paracrine cytoprotective action. Furthermore, we have ...

Reperfusion injury may cause myocardial cell death and limit the benefit achieved by restoration of coronary artery patency in patients with acute myocardial infarction. The mechanism includes altered Ca(2+) handling with cytosolic and mitochondrial Ca(2+) overload, Ca(2+)- and ATP-dependent hypercontraction, cytoskeletal fragility, mitochondrial permeability transition and gap junction-mediated propagation of ...

Stem cell transplantation is a promising approach for treatment of the postinfarcted heart and prevention of deleterious cardiac remodeling and heart failure. We explored this issue by transplanting mouse C2C12 myoblasts, genetically engineered to express enhanced green fluorescent protein (eGFP) or eGFP and relaxin (eGFP/RLX), into swine with chronic myocardial ...

Despite previous studies demonstrating a cardioprotective role of estradiol via its estrogen receptor (ER)alpha, the underlying mechanisms remain unclear. Here we aimed to define ERalpha-involved mechanisms against cardiac injury. Seven days after myocardial infarction in male rats, cardiac ERalpha was upregulated in post-infarct cardiac c-kit+ cells accumulating in periinfarct myocardium ...

BACKGROUND: Clinical studies on intracoronary stem cell infusion in patients with acute myocardial infarction (AMI) have shown promising results for left ventricular ejection fraction (LVEF). However, preclinical studies have shown that intramyocardial cell injection is better than the intracoronary approach. OBJECTIVE: To test safety and feasibility of intramyocardial cell injection ...