scholarly journals Ingenuity Pathway Analysis of the Human Cardiac Cell Atlas Identifies Differences Between Right and Left Ventricular Cardiomyocytes

2021 ◽  
Author(s):  
Sasha Z. Prisco ◽  
Felipe Kazmirczak ◽  
Thenappan Thenappan ◽  
Kurt W. Prins
Keyword(s):  
Ingenuity Pathway Analysis ◽  
Pathway Analysis ◽  
Left Ventricular ◽  
Cardiac Cell ◽  
Ventricular Cardiomyocytes

Stereological characterization of left ventricular cardiomyocytes, capillaries, and innervation in the nondiabetic, obese mouse

2012 ◽  
Vol 21 (4) ◽  
pp. 346-354 ◽  
Author(s):  
Carina Gruber ◽  
Karin Kohlstedt ◽  
Annemarieke E. Loot ◽  
Ingrid Fleming ◽  
Wolfgang Kummer ◽  
...  
Keyword(s):  
Left Ventricular ◽  
Obese Mouse ◽  
Ventricular Cardiomyocytes

scholarly journals Chronic Alcohol Consumption Blunts β-Adrenergic Responsiveness in Left Ventricular Cardiomyocytes

2010 ◽  
Vol 98 (3) ◽  
pp. 518a
Author(s):  
Krista N. Blackwell ◽  
Dennis J. Rozanski ◽  
Dominique C. Renard-Rooney ◽  
Andrew P. Thomas
Keyword(s):  
Alcohol Consumption ◽  
Left Ventricular ◽  
Chronic Alcohol ◽  
Chronic Alcohol Consumption ◽  
Ventricular Cardiomyocytes

scholarly journals Serotonin increases L-type Ca2+ current and SR Ca2+ content through 5-HT4 receptors in failing rat ventricular cardiomyocytes

2007 ◽  
Vol 293 (4) ◽  
pp. H2367-H2376 ◽  
Author(s):  
Jon Arne Kro Birkeland ◽  
Fredrik Swift ◽  
Nils Tovsrud ◽  
Ulla Enger ◽  
Per Kristian Lunde ◽  
...  
Keyword(s):  
Myosin Light Chain ◽  
Troponin I ◽  
Contractile Function ◽  
Left Ventricular ◽  
Inotropic Response ◽  
Receptor Stimulation ◽  
Ventricular Cardiomyocytes ◽  
Myosin Light Chain 2 ◽  
Intracellular Ca ◽  
Male Wistar Rats

Rats with congestive heart failure (CHF) develop ventricular inotropic responsiveness to serotonin (5-HT), mediated through 5-HT2A and 5-HT4 receptors. Human ventricle is similarly responsive to 5-HT through 5-HT4 receptors. We studied isolated ventricular cardiomyocytes to clarify the effects of 5-HT on intracellular Ca2+ handling. Left-ventricular cardiomyocytes were isolated from male Wistar rats 6 wk after induction of postinfarction CHF. Contractile function and Ca2+ transients were measured in field-stimulated cardiomyocytes, and L-type Ca2+ current ( ICa,L) and sarcoplasmic reticulum (SR) Ca2+ content were measured in voltage-clamped cells. Protein phosphorylation was measured by Western blotting or phosphoprotein gel staining. 5-HT4- and 5-HT2A-receptor stimulation induced a positive inotropic response of 33 and 18% (both P < 0.05) and also increased the Ca2+ transient (44 and 6%, respectively; both P < 0.05). ICa,L and SR Ca2+ content increased only after 5-HT4-receptor stimulation (57 and 65%; both P < 0.05). Phospholamban serine16 (PLB-Ser16) and troponin I phosphorylation increased by 26 and 13% after 5-HT4-receptor stimulation ( P < 0.05). 5-HT2A-receptor stimulation increased the action potential duration and did not significantly change the phosphorylation of PLB-Ser16 or troponin I, but it increased myosin light chain 2 (MLC2) phosphorylation. In conclusion, the positive inotropic response to 5-HT4 stimulation results from increased ICa,L and increased phosphorylation of PLB-Ser16, which increases the SR Ca2+ content. 5-HT4 stimulation is thus, like β-adrenoceptor stimulation, possibly energetically unfavorable in CHF. 5-HT2A-receptor stimulation, previously studied in acute CHF, induces a positive inotropic response also in chronic CHF, probably mediated by MLC2 phosphorylation.

Abstract 372: MicroRNA-9 Inhibits Hyperglycemia-induced Cardiac Pyroptosis by Targeting ELAVL1

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Prince Jeyabal ◽  
Rajarajan A Thandavarayan ◽  
Darukeshwara Joladarashi ◽  
Sahana Suresh Babu ◽  
Shashirekha Krishnamurthy ◽  
...  
Keyword(s):  
Heart Failure ◽  
High Glucose ◽  
Cardiac Tissue ◽  
Critical Role ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Therapeutic Implications ◽  
Caspase 1 ◽  
Ventricular Cardiomyocytes ◽  
Nlrp3 Expression

Diabetic cardiomyopathy is a common complication in patients with diabetes and is associated with underlying chronic inflammation and cardiac cell death, subsequently leading to left ventricular dysfunction and heart failure. ELAV-like protein 1 (ELAVL1, mRNA stabilizing protein) and NLRP3 activation (inflammasome complex protein)-mediated IL-1beta synthesis play a critical role in the progression of heart failure. However, ELAVL1 regulation of pyroptosis (caspase-1-mediated programmed apoptosis) and associated IL-1beta release in cardiomyocytes, especially under diabetic condition, remains elusive. Human diabetic, non-diabetic heart tissues, human ventricular cardiomyocytes and rat cardiomyoblasts exposed to high glucose (HG) were used for our studies. Our data demonstrates that human ventricular cardiomyocytes exposed to high glucose condition showed significant increase in ELAVL1 and NLRP3 expression with a concomitant increase in caspase-1 and IL-1 beta expression. Furthermore, human cardiac tissue from diabetic patients showed increased ELAVL1, caspase-1 and NLRP3 expression as compared to non-diabetic hearts. Intriguingly, ELAVL1 knockdown abrogates TNF-α induced canonical pyroptosis via NLRP3, caspase-1 and IL-1beta suppression. Interestingly, miRNA-9 expression significantly reduces in high glucose treated cardiomyocytes and in human diabetic hearts. Bioinformatics analysis and target validation assays showed that miR-9 directly targets ELAVL1. Inhibition of miR-9 up regulates ELAVL1 expression and activates caspase-1. Alternatively, miR-9 mimics attenuate hyperglycemia-induced ELAVL1 and inhibit cardiomyocyte pyroptosis. To our knowledge, this is the first report to demonstrate the role of miR-9/ELAVL1 in hyperglycemia-induced cardiac pyroptosis. Taken together our study highlights the potential therapeutic implications in preventing cardiomyocyte cell loss in human diabetic failing heart.

Clinically Translatable Prevention of Anthracycline Cardiotoxicity by Dexrazoxane Is Mediated by Topoisomerase II Beta and Not Metal Chelation

2021 ◽  
Author(s):  
Eduard Jirkovský ◽  
Anna Jirkovská ◽  
Hana Bavlovič-Piskáčková ◽  
Veronika Skalická ◽  
Zuzana Pokorná ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Topoisomerase Ii ◽  
Left Ventricular ◽  
Functional Markers ◽  
Metal Chelation ◽  
Anthracycline Cardiotoxicity ◽  
Ventricular Cardiomyocytes ◽  
Cardioprotective Effects ◽  
Topoisomerase Ii Beta

Background: Anthracycline-induced heart failure has been traditionally attributed to direct iron-catalyzed oxidative damage. Dexrazoxane (DEX)—the only drug approved for its prevention—has been believed to protect the heart via its iron-chelating metabolite ADR-925. However, direct evidence is lacking, and recently proposed TOP2B (topoisomerase II beta) hypothesis challenged the original concept. Methods: Pharmacokinetically guided study of the cardioprotective effects of clinically used DEX and its chelating metabolite ADR-925 (administered exogenously) was performed together with mechanistic experiments. The cardiotoxicity was induced by daunorubicin in neonatal ventricular cardiomyocytes in vitro and in a chronic rabbit model in vivo (n=50). Results: Intracellular concentrations of ADR-925 in neonatal ventricular cardiomyocytes and rabbit hearts after treatment with exogenous ADR-925 were similar or exceeded those observed after treatment with the parent DEX. However, ADR-925 did not protect neonatal ventricular cardiomyocytes against anthracycline toxicity, whereas DEX exhibited significant protective effects (10–100 µmol/L; P <0.001). Unlike DEX, ADR-925 also had no significant impact on daunorubicin-induced mortality, blood congestion, and biochemical and functional markers of cardiac dysfunction in vivo (eg, end point left ventricular fractional shortening was 32.3±14.7%, 33.5±4.8%, 42.7±1.0%, and 41.5±1.1% for the daunorubicin, ADR-925 [120 mg/kg]+daunorubicin, DEX [60 mg/kg]+daunorubicin, and control groups, respectively; P <0.05). DEX, but not ADR-925, inhibited and depleted TOP2B and prevented daunorubicin-induced genotoxic damage. TOP2B dependency of the cardioprotective effects was probed and supported by experiments with diastereomers of a new DEX derivative. Conclusions: This study strongly supports a new mechanistic paradigm that attributes clinically effective cardioprotection against anthracycline cardiotoxicity to interactions with TOP2B but not metal chelation and protection against direct oxidative damage.

Abstract P215: β3-Adrenergic Receptor Mediated NOS Signaling in Cardiomyocytes

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Vabren L Watts ◽  
Xiaolin Niu ◽  
Karen L Miller ◽  
Lili A Barouch
Keyword(s):  
Molecular Mechanisms ◽  
Pressure Overload ◽  
Fold Increase ◽  
Left Ventricular ◽  
Neonatal Rat ◽  
Regulatory Site ◽  
Ventricular Cardiomyocytes ◽  
Unstimulated Control ◽  
Key Factor ◽  
Nos Isoforms

Beta3 -adrenergic receptors play a pivotal role in modulating cardiac function, though their precise role in the heart remains controversial. We have recently demonstrated alterations in Ca 2+ -dependent NOS isoforms and decreased NOS activity in left ventricular tissue of beta3 -/- mice after pressure overload. However, the exact manner in which beta3-AR signaling regulates these isoforms to stimulate NOS activity at the cardiomyocyte level is not well understood. In this study we used a specific beta3-AR agonist, BRL37344 (BRL), to assess the role of beta3-AR in eNOS and nNOS regulation in hypertrophied isolated neonatal rat ventricular cardiomyocytes (NRVM). To induce hypertrophy we pretreated cells with norepinephrine for 72 hours, which resulted in a 70% increase in cell size and a 25% increase in beta3-AR mRNA expression as compared with non-hypertrophied cells, analyzed by immunocytochemistry and real-time PCR. In hypertrophied cardiomyocytes, BRL administration lead to a time-dependent 5-fold increase in NOS activity, measured by the arginine-to-citrulline conversion assay. beta3-activation also caused a 1.5-fold increase in nNOS phosphorylation at positive regulatory site Ser1416, and dephosphorylation of negative regulatory site Ser847 as compared with unstimulated control. NOS activity and nNOS phosphorylation overlapped in time. In addition BRL induced phosphorylation eNOS-Ser114, which indicates eNOS deactivation. Pretreatment with pertussis toxin (PTX) suppressed BRL-induced nNOS-Ser1416 phosphorylation, nNOS-Ser847 dephosphorylation, and NOS activity, suggesting G i/o dependency. Taken together, our data suggest that BRL regulates NOS signaling in ventricular cardiomyocytes via phosphorylation regulation of nNOS. To our knowledge this is first study to demonstrate a role for nNOS phosphorylation as a key factor in beta3-AR signaling. These results contribute significantly to our understanding the negative inotropic properties of myocardial beta3-AR at cellular levels during cardiac sympathetic overstimulation, and will ultimately aid in drug discoveries that target the molecular mechanisms associated heart failure.

Sign in / Sign up

Export Citation Format

Share Document