Myocyte-specific overexpressing HDAC4 promotes myocardial ischemia/reperfusion injury.

Background: Histone deacetylases (HDACs) play a critical role in modulating myocardial protection and cardiomyocyte survivals. However, Specific HDAC isoforms in mediating myocardial ischemia/reperfusion injury remain currently unknown. We used cardiomyocyte-specific overexpression of active HDAC4 to determine the functional role of activated HDAC4 in regulating myocardial ischemia and reperfusion in isovolumetric perfused hearts.

TLR3 Mediates Repair and Regeneration of Damaged Neonatal Heart through Glycolysis Dependent YAP1 Regulated miR-152 Expression.

The present study investigated whether TLR3 is required for neonatal heart repair and regeneration following myocardial infarction (MI). TLR3 deficient neonatal mice exhibited impaired cardiac functional recovery and a larger infarct size, while wild type neonatal mice showed cardiac functional recovery and small infarct size after MI. The data suggest that TLR3 is essential for the regeneration and repair of damaged neonatal myocardium.

Enhanced Glycolytic Metabolism Contributes to Cardiac Dysfunction in Polymicrobial Sepsis.

Background: Cardiac dysfunction is present in >40% of sepsis patients and is associated with mortality rates of up to 70%. Recent evidence suggests that glycolytic metabolism plays a critical role in host defense and inflammation. Activation of Toll-like receptors on immune cells can enhance glycolytic metabolism.

MicroRNA-214 protects against hypoxia/reoxygenation induced cell damage and myocardial ischemia/reperfusion injury via suppression of PTEN and Bim1 expression.

Background: Myocardial apoptosis plays an important role in myocardial ischemia/reperfusion (I/R) injury. Activation of PI3K/Akt signaling protects the myocardium from I/R injury. This study investigated the role of miR-214 in hypoxia/reoxygenation (H/R)-induced cell damage in vitro and myocardial I/R injury in vivo.

MicroRNA-125b Prevents Cardiac Dysfunction in Polymicrobial Sepsis by Targeting TRAF6-Mediated Nuclear Factor κB Activation and p53-Mediated Apoptotic Signaling.

Background:  This study examined the effect of microRNA-125b (miR-125b) on sepsis-induced cardiac dysfunction.

Methods:  Mouse hearts were transfected with lentivirus expressing miR-125b (LmiR-125b) 7 days before cecal ligation and puncture (CLP)-induced sepsis. Cardiac function was examined by echocardiography before and 6 hours after CLP (n = 6/group).

Attenuation of cardiac dysfunction and remodeling of myocardial infarction by microRNA-130a are mediated by suppression of PTEN and activation of PI3K dependent signaling.

Objective: Activation of PI3K/Akt signaling protects the myocardium from ischemia/reperfusion injury. MicroRNAs have been demonstrated to play an important role in the regulation of gene expression at the post-transcriptional level. In this study, we examined whether miR-130a will attenuate cardiac dysfunction and remodeling after myocardial infarction (MI) via PI3K/Akt dependent mechanism.

Attenuation of Cardiac Dysfunction in Polymicrobial Sepsis by MicroRNA-146a Is Mediated via Targeting of IRAK1 and TRAF6 Expression.

Cardiac dysfunction is a major consequence of sepsis/septic shock and contributes to the high mortality of sepsis. Innate and inflammatory responses mediated by TLRs play a critical role in sepsis-induced cardiac dysfunction. MicroRNA-146 (miR-146) was first identified as a negative regulator in innate immune and inflammatory responses induced by LPS.

Poly (I:C) therapy decreases cerebral ischaemia/reperfusion injury via TLR3-mediated prevention of Fas/FADD interaction.

Toll-like receptor (TLR)-mediated signalling plays a role in cerebral ischaemia/reperfusion (I/R) injury. Modulation of TLRs has been reported to protect against cerebral I/R injury. This study examined whether modulation of TLR3 with poly (I:C) will induce protection against cerebral I/R injury.

Toll-like receptor 4 plays a central role in cardiac dysfunction during trauma hemorrhage shock.

Cardiac dysfunction is a major consequence that contributes to the high mortality of trauma-hemorrhage (TH) patients. Recent evidence suggests that innate immune and inflammatory responses mediated by Toll-like receptors (TLRs) play a critical role in the pathophysiologic mechanisms of acute organ dysfunction during TH. This study investigated the role of TLR4 in cardiac dysfunction following TH.

Toll-like receptor 3 plays a role in myocardial infarction and ischemia/reperfusion injury.

Innate immune and inflammatory responses mediated by Toll like receptors (TLRs) have been implicated in myocardial ischemia/reperfusion (I/R) injury. This study examined the role of TLR3 in myocardial injury induced by two models, namely, myocardial infarction (MI) and I/R. First, we examined the role of TLR3 in MI.

Microvascular architecture of mouse urinary bladder described with vascular corrosion casting, light microscopy, SEM, and TEM.

The urinary bladder is a unique organ in that its normal function is storage and release of urine, and vasculature in its wall exhibits specialized features designed to accommodate changes in pressure with emptying and filling. Although we have previously described the fine details of the microvasculature of the urinary bladder of the rabbit and dog, information on the fine details of the microvasculature of the mouse bladder were deemed to be of value because of the increasing use of this species in developing genetic models for studying human disorders. The present study shows that many of the special features of the microvasculature of the mouse urinary bladder are similar to those described in the rabbit and dog, including vessel coiling, abundant collateral circulation, arterial sphincters, and a dense mucosal capillary plexus.

Skeletal muscle stem cells.

Skeletal muscle satellite cells (myoblasts) are the primary stem cells of skeletal muscle which contribute to growth, maintenance, and repair of the muscles. Satellite cells are the first stem cells used for cellular cardiomyoplasty more than 20 years ago. The isolation, culture, labeling, and identification of satellite cells are described in detail here.

Cellular cardiomyoplasty: its past, present, and future.

Cellular cardiomyoplasty is a cell therapy using stem cells or progenitor cells for myocardial regeneration to improve cardiac function and mitigate heart failure. Since we first published cellular cardiomyoplasty in 1989, this procedure became the innovative method to treat damaged myocardium other than heart transplantation. A significant improvement in cardiac function, metabolism, and perfusion is generally observed in experimental and clinical studies, but the improvement is mild and incomplete.

Activation of myocardial phosphoinositide-3-kinase p110α ameliorates cardiac dysfunction and improves survival in polymicrobial sepsis.

Phosphoinositide-3-kinase (PI3K)/Akt dependent signaling has been shown to improve outcome in sepsis/septic shock. There is also ample evidence that PI3K/Akt dependent signaling plays a crucial role in maintaining normal cardiac function. We hypothesized that PI3K/Akt signaling may ameliorate septic shock by attenuating sepsis-induced cardiac dysfunction.

CpG-ODN, the TLR9 agonist, attenuates myocardial ischemia/reperfusion injury: involving activation of PI3K/Akt signaling.

Background: Toll-like receptors (TLRs) have been implicated in myocardial ischemia/reperfusion (I/R) injury. The TLR9 ligand, CpG-ODN has been reported to improve cell survival. We examined effect of CpG-ODN on myocardial I/R injury.

Toll-like receptor 3 plays a central role in cardiac dysfunction during polymicrobial sepsis.

Objective: To determine the role of Toll-like receptor 3 in cardiac dysfunction during polymicrobial sepsis.

Design: Controlled animal study.

Setting: University research laboratory.

Scavenger receptor A (SR-A) is required for LPS-induced TLR4 mediated NF-κB activation in macrophages.

Recent evidence suggests that the macrophage scavenger receptor class A (SR-A, aka, CD204) plays a role in the induction of innate immune and inflammatory responses. We investigated whether SR-A will cooperate with Toll-like receptors (TLRs) in response to TLR ligand stimulation. Macrophages (J774/a) were treated with Pam2CSK4, (TLR2 ligand), Polyinosinic:polycytidylic acid (Poly I:C) (TLR3 ligand), and Lipopolysaccharides (LPS) (TLR4 ligand) for 15 min in the presence or absence of fucoidan (the SR-A ligand).

The toll-like receptor 9 agonist, CpG-oligodeoxynucleotide 1826, ameliorates cardiac dysfunction after trauma-hemorrhage.

Cardiovascular collapse is the major factor contributing to the mortality of trauma-hemorrhage (T-H) patients. Toll-like receptors (TLRs) play a critical role in T-H-induced cardiac dysfunction. This study evaluated the role of TLR9 agonist, CpG-oligodeoxynucleotide (ODN) 1826, in cardiac functional recovery after T-H.

TLR2 ligand induces protection against cerebral ischemia/reperfusion injury via activation of phosphoinositide 3-kinase/Akt signaling.

This study examined the effect of TLR2 activation by its specific ligand, Pam3CSK4, on cerebral ischemia/reperfusion (I/R) injury. Mice (n = 8/group) were treated with Pam3CSK4 1 h before cerebral ischemia (60 min), followed by reperfusion (24 h). Pam3CSK4 was also given to the mice (n = 8) 30 min after ischemia.

Glucan phosphate attenuates myocardial HMGB1 translocation in severe sepsis through inhibiting NF-κB activation.

Myocardial dysfunction is a major consequence of septic shock and contributes to the high mortality of sepsis. High-mobility group box 1 (HMGB1) serves as a late mediator of lethality in sepsis. We have reported that glucan phosphate (GP) attenuates cardiac dysfunction and increases survival in cecal ligation and puncture (CLP)-induced septic mice.

Toll-like receptors: new players in myocardial ischemia/reperfusion injury.

Innate immune and inflammatory responses have been implicated in myocardial ischemia/reperfusion (I/R) injury. However, the mechanisms by which innate immunity and inflammatory response are involved in myocardial I/R have not been elucidated completely. Recent studies highlight the role of Toll-like receptors (TLRs) in the induction of innate immune and inflammatory responses.

Scavenger receptor class-A has a central role in cerebral ischemia-reperfusion injury.

The innate immune response is involved in the pathophysiology of cerebral ischemia-reperfusion (I/R) injury. Recent evidence suggests that scavenger receptors have a role in the induction of innate immunity. In this study, we examined the role of scavenger receptor A (SR-A) in focal cerebral I/R injury.

TLR2 ligands induce cardioprotection against ischaemia/reperfusion injury through a PI3K/Akt-dependent mechanism.

Aims: Toll-like receptor (TLR)-mediated signalling pathways have been implicated in myocardial ischaemia/reperfusion (I/R) injury. Activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway protects the myocardium from ischaemic injury. We hypothesized that the modulation of TLR2 would induce cardioprotection against I/R injury via activation of the PI3K/Akt signalling.

TLR2 ligands attenuate cardiac dysfunction in polymicrobial sepsis via a phosphoinositide 3-kinase-dependent mechanism.

Myocardial dysfunction is a major consequence of septic shock and contributes to the high mortality of sepsis. In the present study, we examined the effect of Toll-like receptor 2 (TLR2) ligands, peptidoglycan (PGN), and Pam3CSK4 (Pam3) on cardiac function in cecal ligation and puncture (CLP)-induced sepsis in mice. We also investigated whether the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is involved in the effect of TLR2 ligands on cardiac function in CLP mice.

Cellular cardiomyoplasty: what have we learned?

Restoring blood flow, improving perfusion, reducing clinical symptoms, and augmenting ventricular function are the goals after acute myocardial infarction. Other than cardiac transplantation, no standard clinical procedure is available to restore damaged myocardium. Since we first reported cellular cardiomyoplasty in 1989, successful outcomes have been confirmed by experimental and clinical studies, but definitive long-term efficacy requires large-scale placebo-controlled double-blind randomized trials.