Abstract 1372: Characterization Of The Rejuvenation Of Cardiac Sympathetic Nerves In Cardiac Hypertrophy

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Kensuke Kimura ◽  
Masaki Ieda ◽  
Hideaki Kanazawa ◽  
Takahide Arai ◽  
Takashi Kawakami ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Fluorescent Protein ◽  
Sympathetic Neurons ◽  
Weight Ratio ◽  
Sympathetic Nerves ◽  
Marker Genes ◽  
List Type ◽  
Stellate Ganglia ◽  
Immature Neuron

Background : Cardiac hypertrophy induces the fetal isoform of genes (rejuvenation), including contractile proteins, ion channels, and natriuretic peptides. Cardiac sympathetic nerve function is known to be altered in cardiac hypertrophy and congestive heart failure. We recently reported that alteration of cardiac sympathetic nerves (CSN) was caused by their rejuvenation (Circ Res, 2007). The present study was designed to examine the precise characterization of the rejuvenation of CSN in cardiac hypertrophy. Methods and Results : RV hypertrophy was produced by consistent hypoxia (10% O 2 ) in C57/BL6 mice. RV pressure increased to 47 mmHg, and RV/(body weight) ratio increased by 1.6 fold. Nerve growth factor protein was augmented in hypertrophic RV, but was unchanged in LV. Double-transgenic mice, which specifically express eGFP (enhanced green fluorescent protein) in the sympathetic neurons, was generated by crossing dopamine β-hydroxylase (DBH)-Cre mice with Floxed-eGFP mice. The eGFP-positive CSN were markedly increased in hypertrophic RV, but not in LV. Nerve density, quantitated by immunostained area with eGFP and GAP43 (growth-associated corn marker), increased by 8.1 and 9.3 fold, respectively, in RV, but not in LV. (4) Catecholamine content was attenuated in RV. (5) Western blot revealed that tyrosine hydroxylase was markedly down-regulated in RV. (6) Immunostaining clearly demonstrated that the immature neuron markers, PSA-NCAM (highly polysialylated neural cell adhesion molecule) and Ulip-1 (Unc-33-like phosphoprotein 1), were expressed in CSN in hypertrophic RV and stellate ganglia. Basic helix-loop-helix transcription factor, Mash-1 (mammalian achaete-scute complex homolog 1) was strongly expressed in the stellate ganglia. (7) Immature neuron marker-immunopositive cells in stellate ganglia had a markedly decreased TH expression. Conclusion : The rejuvenated CSN showed various immature and fetal neuron marker genes at not only the peripheral axons but also the cellular bodies at the stellate ganglia. Rejuvenation of CSN might be critically involved in the alteration of sympathetic neuronal function in cardiac hypertrophy, including depressed norepinephrine synthesis and hyperinnervation.

scholarly journals Novel target identification using single cell sequencing and electrophysiology of cardiac sympathetic neurons in disease

2019 ◽  
Author(s):  
Harvey Davis ◽  
Neil Herring ◽  
David J Paterson
Keyword(s):  
Single Cell ◽  
Target Identification ◽  
Sodium Current ◽  
Sympathetic Neurons ◽  
Sympathetic Nerves ◽  
Underlying Mechanism ◽  
Neuronal Firing ◽  
Surgical Removal ◽  
Spontaneously Hypertensive ◽  
Stellate Ganglia

AbstractThe activity of cardiac sympathetic nerves from the stellate ganglia is increased in many cardiovascular diseases contributing to the pathophysiology, however the mechanisms underlying this are unknown. Moreover, clinical studies show their surgical removal is an effective treatment, despite the biophysical properties of these neurons being largely unstudied. Here we demonstrate that stellate ganglia neurons from prehypertensive spontaneously hypertensive rats are hyperactive and describe in detail their electrophysiological phenotype guided by single cell RNA-sequencing, molecular biology and perforated patch-clamp to uncover the underlying mechanism. The expression of key transcripts was confirmed in human stellate ganglia. We further demonstrate the contribution of a plethora of ion channels to stellate ganglia neuronal firing, and show that hyperexcitability was curbed by M-current activators, non-selective sodium current blockers or inhibition of Nav1.1-1.3, Nav1.6 or INaP. These findings have implications for target discovery to reduce cardiac sympathetic activity without resorting to surgery.

Abstract 65: Regulation of Cardiac Hypertrophy and Dilated Cardiomyopathy by CIP

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Zhan-Peng Huang ◽  
Masaharu Kataoka ◽  
Jinghai Chen ◽  
Da-Zhi Wang
Keyword(s):  
Transgenic Mice ◽  
Cardiac Hypertrophy ◽  
Dilated Cardiomyopathy ◽  
Cardiac Development ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Premature Death ◽  
Marker Genes ◽  
Ontology Term ◽  
Hypertrophic Growth

Cardiac hypertrophy is one of the primary responses of the heart to pathophysiological stress. However, the mechanism of the transition from compensative hypertrophic growth to cardiac dilation is poor understood. Recently, we identified a cardiac-specific expressed gene CIP. The expression of CIP is unchanged in hypertrophic heart but significantly down-regulated in dilated hearts, suggesting CIP may play an important role in the transition from cardiac hypertrophy to dilated cardiomyopathy. We generated CIP knockout mice and found that CIP is dispensable for cardiac development. Interestingly, CIP-null mutant mice developed severe cardiac dilation 4 weeks after TAC (transverse aortic constriction) surgery, while control mice were still at the stage of compensative hypertrophic growth. Echocardiography and histological examinations showed that mutant hearts had enlarged chamber with thinner ventricle wall and decreased cardiac performance compared to controls. The expression of marker genes of cardiac disease, BNP and Myh7, was elevated. Consistently, deletion of CIP in Myh6-CnA transgenic mice result in premature death, displaying severe left ventricle dilation. Conversely, cardiac-specific CIP overexpression inhibited pressure overload-induced cardiac hypertrophy. CIP transgenic mice exhibit decreased ventricle weight/body weight ratio, decreased cardiomyocyte cross-section area and repressed expression of hypertrophic related marker genes. CIP overexpression also protected the heart from developing cardiac dilation and preserved the cardiac function after prolonged pressure overload. We performed unbiased microarray assay to document the transcriptome in CIP knockout and control mice which were subjected to pressure overload (TAC). The analysis of Gene Ontology term indicated the Negative Regulation of Apoptosis was down-regulated while the Collagen/Extracellular Structure Organization was up-regulated in CIP-null hearts under TAC condition. In summary, our studies established CIP as a key regulator of the transition from cardiac hypertrophy to dilated cardiomyopathy. The protective effect of CIP in cardiac remodeling indicates that CIP could become a therapeutic target for cardiac diseases.

Abstract 241: Cardiac-Specific Overexpression of Runx2 Mediates Cardiac Hypertrophy and Dysfunction in Mice

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Hiroyuki Nakayama ◽  
Tatsuto Hamatani ◽  
Shohei Kumagai ◽  
Kota Tonegawa ◽  
Tomomi Yamashita ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Premature Death ◽  
Heart Weight ◽  
Pcr Analysis ◽  
Marker Genes ◽  
Hypertrophic Response ◽  
Neonatal Cardiomyocytes

Backgrounds: Recent studies demonstrated that the osteopontin (OPN), an acid phosphoprotein plays pivotal roles in cardiac hypertrophy and failure. An osteogenic transcription factor Runx2 regulates the expression of OPN in osteoblasts. In the present study, we examined the pathological role of Runx2 in cardiac hypertrophy and failure. Methods and Results: Runx2 expression was detected in neonatal cardiomyocytes and upregulated in heart 14 days after myocardial infarction (MI) as well as 7days after transverse aortic constriction (TAC) procedures. To determine the functional role of Runx2 in heart, we generated transgenic mice (TG) with inducible cardiac-specific overexpression of Runx2. Two TG lines (low and high) were obtained and high-expressing TG (HE-TG) showed premature death within 8 weeks of age specifically in male mice. At two months of age, the survived male and female HE-TG displayed significant increases in heart weight/body weight ratio (mg/g) compared to controls (control; 4.95±0.26, n=6 vs HE-TG; 6.63±0.12, n=5, p<.05). Consistent with those results, the expression of hypertrophic marker genes such as atrial natriuretic factor (ANF) and αskeletal actin significantly increased in HE-TG heart assessed by real-time RT-PCR analysis. In addition, HE-TG mice demonstrated decreased fractional shortening assessed by echocardiography (control; 44.1±1.89%, n=9 vs HE-TG; 23.9±3.48%, n=7, p<.05). HE-TG mice demonstrated significantly lower heart rate (control; 630±18 bpm, vs HE-TG; 350±74 bpm, n=3 each, p<.05) and complete atrioventricular block by telemetry analysis. In response to pressure overload, low expressing TG (LE-TG) demonstrated higher mortality and enhanced cardiac hypertrophic response after TAC (control; 6.20±0.23, n=6 vs LE-TG; 6.90±0.26, n=4, p<.05). Conclusions: Targeted expression of Runx2 in heart mediates cardiac dysfunction and hypertrophy in mice. Thus, Runx2 could be a novel therapeutic target for heart failure.

scholarly journals Altered spatio-specific CaMKII activation in autophagy deficient mice

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
J Voglhuber ◽  
M Abdellatif ◽  
N Djalinac ◽  
V Trummer-Herbst ◽  
S Ljubojevic-Holzer ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Nuclear Envelope ◽  
Exercise Tolerance ◽  
Acute Stress ◽  
Weight Ratio ◽  
Marker Genes ◽  
Cardiac Reserve ◽  
Camkii Activation ◽  
Deficient Mice

Abstract Background Autophagy is linked to preventing the development of cardiac hypertrophy and failure. While aberrant activation of Ca2+/calmodulin-dependent kinase II (CaMKII) promotes myocardial remodeling, the role of autophagy in maintaining cardiac Ca2+ homeostasis and regulating CaMKII signaling is unknown. Objective To test whether loss of autophagy promotes subcellular alterations in CaMKII activation in early myocardial remodelling, and whether compromised in vivo cardiac function parallels those changes. Methods Young (10–15 weeks) cardiomyocyte-specific autophagy protein 5-deficient mice (Atg5−/−) mice and their littermate controls (Atg5+/+) underwent comprehensive in vivo phenotyping using echocardiography, exercise tolerance and hemodynamic stress testing. In vitro assessment included gravimetry, qPCR of hypertrophy marker genes and cellular and nuclear dimensions of isolated ventricular myocytes. CaMKII activation was studied by immunocytochemistry in cardiomyocytes upon exposure to basal (1Hz) or high (4Hz) pacing frequency. Autophosphorylated CaMKII (pT286) signal was evaluated in different subcellular spaces (i.e. cytoplasm, nucleoplasm and nuclear envelope). Results Before symptomatic cardiac dysfunction occurred, Atg5−/− mice showed compromised cardiac reserve in response to β-adrenergic stimulation (dp/dt max: 9475±126 vs 7364±496 mmHg/s, N=4–5; p=0.041), despite similar maximum heart rate. Consequently, effort intolerance (distance run: 251±22 vs 152±13 m, N=8; p=0.03) and maximal oxygen consumption (2093±66 vs 1763±131 ml/h/kg, N=8; p=0.04) were reduced during treadmill exercise tolerance testing. Increased heart-to-body weight ratio (8.1±0.5 vs 10.2±0.8 N=9; p=0.017) was associated with elevated mRNA expression of hypertrophy marker NppB (278% of Atg5+/+, N=5; p=0.016) in Atg5−/− mice, which showed enlarged cardiomyocytes and nuclei, as width-to-length ratio. Because Atg5−/− cardiomyocytes exhibit elevated nuclear Ca2+ levels at high pacing frequency, we now measured subcellular CaMKII activation under the same experimental conditions. Interestingly, at 1Hz, p-CaMKII was increased specifically at the nuclear envelope (154% of Atg5+/+, N=5 mice, 153–159 cells; p=0.029), but not in the cytoplasm or nucleoplasm. Increasing pacing frequency to 4Hz did not alter p-CaMKII levels in Atg5+/+ cells. However, p-CaMKII was increased by ∼30% and ∼20% in the cytoplasm and nucleoplasm of Atg5−/− cells respectively (N=5 mice, 153–155 cells). Conclusion Loss of ATG5-dependent autophagy causes cardiac hypertrophy and impaired cardiac reserve upon acute stress, which involves CaMKII activation, likely through the imbalance of nuclear Ca2+ load. Although, selective increase in p-CaMKII at the nuclear envelope in Atg5−/− mice may temporarily protect from nuclear Ca2+ overload, excessive CaMKII activation in the cytoplasm and the nucleoplasm upon increased workload, likely drives hypertrophic signalling toward heart failure in autophagy-defective mice. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Austrian Science Fund (FWF)

Rheological characterization of tack and viscoelasticity of compositions of crepe coating used in the Yankee dryer

TAPPI Journal ◽  
2019 ◽  
Vol 18 (11) ◽  
pp. 641-649
Author(s):  
JOSHUA OMAMBALA ◽  
CARL MCINTYRE
Keyword(s):  
Normal Force ◽  
Weight Ratio ◽  
Good Combination ◽  
Rheological Characterization ◽  
Nonlinear Viscoelastic ◽  
Coating Composition ◽  
Linear And Nonlinear ◽  
Work Done ◽  
Tissue Production

The vast majority of tissue production uses creping to achieve the required set of properties on the base sheet. The Yankee coating helps to develop the desired crepe that in turn determines properties such as bulk and softness. The adhesion of the sheet to the Yankee surface is a very important characteristic to consider in achieving the desired crepe. The coating mix usually consists of the adhesive, modifier, and release. A good combination of these components is essential to achieving the desired properties of the tissue or towel, which often are determined by trials on the machine that can be time consuming and lead to costly rejects. In this paper, five compositions of an industrial Yankee coating adhesive, modifier, and release were examined rheologically. The weight ratio of the adhesive was kept constant at 30% in all five compositions and the modifier and release ratios were varied. The normal force and work done by the different compositions have been shown at various temperatures simulating that of the Yankee surface, and the oscillatory test was carried out to explain the linear and nonlinear viscoelastic characteristic of the optimal coating composition.

scholarly journals Fabrication and Characterization of Electrospun Poly(acrylonitrile-co-Methyl Acrylate)/Lignin Nanofibers: Effects of Lignin Type and Total Polymer Concentration

Polymers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 992
Author(s):  
Suchitha Devadas ◽  
Saja M. Nabat Al-Ajrash ◽  
Donald A. Klosterman ◽  
Kenya M. Crosson ◽  
Garry S. Crosson ◽  
...  
Keyword(s):  
Methyl Acrylate ◽  
Lignin Content ◽  
Polymer Concentration ◽  
Weight Ratio ◽  
Electrospun Nanofibers ◽  
Polymer Content ◽  
Blend Ratio ◽  
Blend Ratios ◽  
Poly Acrylonitrile

Lignin macromolecules are potential precursor materials for producing electrospun nanofibers for composite applications. However, little is known about the effect of lignin type and blend ratios with synthetic polymers. This study analyzed blends of poly(acrylonitrile-co-methyl acrylate) (PAN-MA) with two types of commercially available lignin, low sulfonate (LSL) and alkali, kraft lignin (AL), in DMF solvent. The electrospinning and polymer blend solution conditions were optimized to produce thermally stable, smooth lignin-based nanofibers with total polymer content of up to 20 wt % in solution and a 50/50 blend weight ratio. Microscopy studies revealed that AL blends possess good solubility, miscibility, and dispersibility compared to LSL blends. Despite the lignin content or type, rheological studies demonstrated that PAN-MA concentration in solution dictated the blend’s viscosity. Smooth electrospun nanofibers were fabricated using AL depending upon the total polymer content and blend ratio. AL’s addition to PAN-MA did not affect the glass transition or degradation temperatures of the nanofibers compared to neat PAN-MA. We confirmed the presence of each lignin type within PAN-MA nanofibers through infrared spectroscopy. PAN-MA/AL nanofibers possessed similar morphological and thermal properties as PAN-MA; thus, these lignin-based nanofibers can replace PAN in future applications, including production of carbon fibers and supercapacitors.

scholarly journals Ectopic atrial arrhythmias arising from canine thoracic veins during in vivo stellate ganglia stimulation

2008 ◽  
Vol 295 (2) ◽  
pp. H691-H698 ◽  
Author(s):  
Alex Y. Tan ◽  
Shengmei Zhou ◽  
Byung Chun Jung ◽  
Masahiro Ogawa ◽  
Lan S. Chen ◽  
...  
Keyword(s):  
Pulmonary Vein ◽  
Sinus Node ◽  
Periodic Acid ◽  
Sympathetic Innervation ◽  
Sympathetic Nerves ◽  
Atrial Arrhythmias ◽  
Periodic Acid Schiff ◽  
Stellate Ganglia ◽  
Ectopic Beats

The purpose of the present study was to determine whether thoracic veins may act as ectopic pacemakers and whether nodelike cells and rich sympathetic innervation are present at the ectopic sites. We used a 1,792-electrode mapping system with 1-mm resolution to map ectopic atrial arrhythmias in eight normal dogs during in vivo right and left stellate ganglia (SG) stimulation before and after sinus node crushing. SG stimulation triggered significant elevations of transcardiac norepinephrine levels, sinus tachycardia in all dogs, and atrial tachycardia in two of eight dogs. Sinus node crushing resulted in a slow junctional rhythm (51 ± 6 beats/min). Subsequent SG stimulation induced 20 episodes of ectopic beats in seven dogs and seven episodes of pulmonary vein tachycardia in three dogs (cycle length 273 ± 35 ms, duration 16 ± 4 s). The ectopic beats arose from the pulmonary vein ( n = 11), right atrium ( n = 5), left atrium ( n = 2), and the vein of Marshall ( n = 2). There was no difference in arrhythmogenic effects of left vs. right SG stimulation (13/29 vs. 16/29 episodes, P = nonsignificant). There was a greater density of periodic acid Schiff-positive cells ( P < 0.05) and sympathetic nerves ( P < 0.05) at the ectopic sites compared with other nonectopic atrial sites. We conclude that, in the absence of a sinus node, thoracic veins may function as subsidiary pacemakers under heightened sympathetic tone, becoming the dominant sites of initiation of focal atrial arrhythmias that arise from sites with abundant sympathetic nerves and periodic acid Schiff-positive cells.

Role of sympathetic nerves during developing cardiac hypertrophy in Grollman hypertensive rats

1987 ◽  
Vol 253 (4) ◽  
pp. H818-H825
Author(s):  
R. J. Tomanek ◽  
D. W. Carlson ◽  
P. J. Palmer ◽  
R. K. Bhatnagar
Keyword(s):  
Cardiac Hypertrophy ◽  
Renovascular Hypertension ◽  
Volume Expansion ◽  
Peripheral Resistance ◽  
Sympathetic Nerves ◽  
Left Ventricular ◽  
Lv Function ◽  
Hypertensive Rats ◽  
Anterior Portion ◽  
Mitochondrial Volume

Peak left ventricular (LV) function, during rapid volume expansion, and cardiocyte structure were studied in rats with developing cardiac hypertrophy in response to Grollman hypertension (1 kidney, 1 figure 8) after chemical sympathectomy with 6-hydroxydopamine. This form of renovascular hypertension led to the same magnitude of hypertrophy in rats with or without sympathectomy. Indices of peak LV function, measured during acute volume expansion, tended to be normal or slightly higher in hypertensive rats than in controls. Sympathectomy in rats with hypertension significantly improved cardiac and stroke indices while decreasing total peripheral resistance at peak cardiac output. Despite similar magnitudes of LV hypertrophy (LVH) in the two hypertensive groups, cardiocytes in sympathectomized rats had higher mitochondrial volume densities and slightly lower myofibrillar volume densities. After regional sympathectomy of the anterior portion of the LV with phenol, mitochondrial volume density increased by 21% in hypertensive rats with LVH. These data indicate that, during the development of LVH in response to renovascular hypertension, sympathetic nerves do not contribute to the magnitude of LVH but may limit improvement in peak LV performance in response to increased preload. However, sympathetic nerves do play a role in the regulation of mitochondrial and myofibril growth.

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