IL-18 cleavage triggers cardiac inflammation and fibrosis upon β-adrenergic insult.

Aims: Rapid over-activation of β-adrenergic receptor (β-AR) upon stress leads to cardiac inflammation, a prevailing factor that underlies heart injury. However, mechanisms by which acute β-AR stimulation induce cardiac inflammation still remain unknown. Here, we set out to identify the crucial role of inflammasome/interleukin (IL)-18 in initiating and maintaining cardiac inflammatory cascades upon β-AR insult.

Metformin attenuates angiotensin II-induced TGFβ1 expression by targeting hepatocyte nuclear factor-4-α.

Background And Purpose: Metformin, a small molecule, antihyperglycaemic agent, is a well-known activator of AMP-activated protein kinase (AMPK) and protects against cardiac fibrosis. However, the underlying mechanisms remain elusive. TGFβ1 is a key cytokine mediating cardiac fibrosis.

Metformin is a novel suppressor for transforming growth factor (TGF)-β1.

Metformin is a widely used first-line antidiabetic drug that has been shown to protect against a variety of specific diseases in addition to diabetes, including cardiovascular disorders, polycystic ovary syndrome, and cancer. However, the precise mechanisms underlying the diverse therapeutic effects of metformin remain elusive. Here, we report that transforming growth factor-β1 (TGF-β1), which is involved in the pathogenesis of numerous diseases, is a novel target of metformin.

Speckle Tracking Based Strain Analysis Is Sensitive for Early Detection of Pathological Cardiac Hypertrophy.

Cardiac hypertrophy is a key pathological process of many cardiac diseases. However, early detection of cardiac hypertrophy is difficult by the currently used non-invasive method and new approaches are in urgent need for efficient diagnosis of cardiac malfunction. Here we report that speckle tracking-based strain analysis is more sensitive than conventional echocardiography for early detection of pathological cardiac hypertrophy in the isoproterenol (ISO) mouse model.

Echocardiographic assessment of β-adrenoceptor stimulation-induced heart failure with reduced heart rate in mice.

1. Chronic injection with the β-adrenoceptor (β-AR) agonist isoproterenol (ISO) has been commonly used as an animal model of β-AR-induced cardiac remodelling and heart failure. This ISO-treated model usually exhibits significantly decreased conscious heart rate (HR).

β-Adrenergic receptors stimulate interleukin-6 production through Epac-dependent activation of PKCδ/p38 MAPK signalling in neonatal mouse cardiac fibroblasts.

BACKGROUND AND PURPOSE IL-6 plays crucial roles in cardiac hypertrophy, cardiac fibrosis and heart failure. Activation of β-adrenoceptors induced IL-6 production in neonatal mouse cardiac fibroblasts (NMCFs) through a G(s) /adenylate cyclase/cAMP/p38 MAPK pathway but independent of PKA. However, how cAMP activates p38 MAPK is still not defined.

Transactivated EGFR mediates α₁-AR-induced STAT3 activation and cardiac hypertrophy.

α(1)-Adrenergic receptor (α(1)-AR) is a crucial mediator of cardiac hypertrophy. Although numerous intracellular pathways have been implicated in α(1)-AR-induced hypertrophy, its precise mechanism remains elusive. We aimed to determine whether α(1)-AR induces cardiac hypertrophy through a novel signaling pathway-α(1)-AR/epidermal growth factor receptor (EGFR)/signal transducer and activator of transcription 3 (STAT3).

Intercellular transportation of quantum dots mediated by membrane nanotubes.

In this work, we reported that the quantum dot (QD) nanoparticles could be actively transported in the membrane nanotubes between cardiac myocytes. Single particle imaging and tracking of QDs revealed that most QDs moved in a bidirectional mode along the membrane nanotubes with a mean velocity of 1.23 mum/s.

Developmental changes in the geometry, function and responsiveness of the mouse heart to beta-adrenergic stimulation as determined by high-resolution echocardiography.

1. The mouse is the preferred species for gene targeting as a tool for research into the heart and heart development. The developmental features of the geometry and function of the heart in young mice are not well defined and cardiac functional responses following stimulation of beta-adrenoceptors have not been investigated.

Metformin attenuates cardiac fibrosis by inhibiting the TGFbeta1-Smad3 signalling pathway.

Aims: The mechanism of the cardioprotective action of metformin is incompletely understood. We determined the role of metformin in cardiac fibrosis and investigated the mechanism.

Methods And Results: Ten-week-old male mice (C57BL/6) were subjected to left ventricular pressure overload by transverse aortic constriction.

Chlorination diversifies Cimicifuga racemosa triterpene glycosides.

Extracts from the roots and rhizomes of black cohosh (Cimicifuga racemosa) are widely used as dietary supplements to alleviate menopausal symptoms. State-of-the-art quality control measures involve phytochemical fingerprinting of the triterpene glycosides for species identification and chemical standardization by HPLC. In the course of developing materials and methods for standardization procedures, the major C.

alpha1-adrenergic receptors activate AMP-activated protein kinase in rat hearts.

To test the hypothesis that AMP-activated protein kinase (AMPK) is possibly the downstream signaling molecule of certain subtypes of adrenergic receptor (AR) in the heart, we evaluated AMPK activation mediated by ARs in H9C2 cells, a rat cardiac source cell line, and rat hearts. The AMPK-alpha subunit and the phosphorylation level of Thr(172)-AMPK-alpha subunit were subjected to Western blot analysis. Osmotic minipumps filled with norepinephrine (NE), phenylephrine (PE) or vehicle [0.

Heterogeneous transportation of alpha1B-adrenoceptor in living cells.

The heterogeneous motion of alpha(1B)-adrenoceptor (alpha(1B)-AR) was visualized in living cells with BODIPY-labeled antagonist of AR by single molecule fluorescence microscopy at high spatial resolution. The moving trajectory was reconstructed by precise localization (better than 20 nm) with a least-square fit of a two-dimensional Gaussian point spread function to each single spot. Trajectory analysis revealed two apparent groups of movements: directed motion and hindered motion.

Mammalian tolloid alters subcellular localization, internalization, and signaling of alpha(1a)-adrenergic receptors.

In the present study, we identified the CUB5 domain of mammalian Tolloid (mTLD) as a novel protein binding to alpha(1A)-adrenergic receptor (AR) using the yeast two-hybrid system. Whereas CUB5 did not couple to either alpha(1B)-AR or alpha(1D)-AR. It was determined that amino acids 322 to 359 of alpha(1A)-AR were the major binding region for CUB5.

Noncanonical cAMP pathway and p38 MAPK mediate beta2-adrenergic receptor-induced IL-6 production in neonatal mouse cardiac fibroblasts.

We previously reported that cardiac fibroblasts, but not cardiomyocytes, are served as the predominant source of IL-6 after isoproterenol stimulation in mouse myocardium. The present study investigated the molecular mechanism of isoproterenol-mediated secretion of IL-6 in mouse cardiac fibroblasts. Treatment of cells with isoproterenol-induced a time-dependent accumulation of IL-6, which was mediated by beta(2)-adrenergic receptor (AR), the preponderant beta-AR subtype in cardiac fibroblasts.

AICAR stimulates IL-6 production via p38 MAPK in cardiac fibroblasts in adult mice: a possible role for AMPK.

Though known as a sensor of energy balance, AMP-activated protein kinase (AMPK) was recently shown to limit damage and apoptotic activity and contribute to the late preconditioning in heart. Interleukin-6 was also reported to involve in anti-apoptosis and cardio-protection in myocardium. Interestingly, both AMPK activity and IL-6 level were increased in response to ischemia, hypertrophy and oxidative stress.

Different roles of alpha1-adrenoceptor subtypes in mediating cardiomyocyte protein synthesis in neonatal rats.

1. Three different alpha1-adrenoceptor subtypes, designated alpha1A, alpha1B and alpha1D, have been cloned and identified pharmacologically in cardiomyocytes. In vitro studies have suggested that alpha1-adrenoceptors play an important role in facilitating cardiac hypertrophy.

alpha1A-adrenergic receptor mediated pressor response to phenylephrine in anesthetized rat.

To determine which subtype of alpha1-adrenergic receptors plays a role in the regulation of blood pressure, with alpha1A-adrenergic receptor-mediated vasoconstriction in perfused hindlimb as a control, we compared the inhibitory effects of various alpha1-adrenergic receptor selective antagonists on the vasopressure responses to phenylephrine between the mean arterial pressure and hindlimb perfusion pressure in anesthetized rats. In Normotensive Wistar rats, the results showed that the inhibitory effects (dose ratios of ED50, Dr) of alpha1-adrenoceptor selective antagonist (prazosin, Dr 13.5+/-3.

[Effects of beta-adrenoceptor activation on metabolism in neonatal rat cardiomyocytes].

The aim of the present study was to investigate the effects of beta-adrenergic receptor (beta-AR) activation on metabolism in cultured neonatal rat cardiomyocytes. The protein synthesis and total protein content of cardiomyocytes were determined by [(3)H]-leucine incorporation and BCA protein content assay. Cardiomyocyte glucose uptake was measured by [(3)H]-2-deoxy-D-glucose uptake analysis.

Functional alpha1-adrenergic receptor subtypes in human right gastroepiploic artery.

Aim: To study the functional alpha1-adrenergic receptor (alpha1-AR) subtypes in human right gastroepiploic artery (RGA).

Methods: The effects of alpha2-AR, alpha1-AR, and alpha1-AR subtype selective antagonists on norepinephrine (NE)-induced vasoconstriction in isolated human RGA were observed by contractile function experiment.

Results: Cumulative concentration-response curves for NE were competitively antagonized in RGA by alpha2-AR selective antagonist yohimbine (pA2 6.

Black cohosh (Cimicifuga racemosa L.) protects against menadione-induced DNA damage through scavenging of reactive oxygen species: bioassay-directed isolation and characterization of active principles.

The roots/rhizomes of Cimicifuga racemosa L. (Nutt.) (black cohosh) have traditionally been used to treat menopausal symptoms through an unknown mechanism of action.