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  • 1
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    Abstract 195: Increases in Ca 2+ Influx through the L-type Ca 2+ Channel Induces Pathological Cardiomyocyte Hypertrophy
    Ovid Technologies (Wolters Kluwer Health) ; 2007
    In:  Circulation Vol. 116, No. suppl_16 ( 2007-10-16)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 116, No. suppl_16 ( 2007-10-16)
    Abstract: Cardiac hypertrophy (LVH) is associated with the development of arrhythmia (sudden cardiac death) and congestive heart failure. While there is a clear role for activation of calcium (Ca) regulated signaling pathways in LVH, the specific role of Ca influx (I Ca ) through the L-type calcium channel (LTCC) has not been directly examined and is the topic of this study. Methods: In vitro, Ca influx into cultured feline (F) and neonatal rat (NR) ventricular myocytes (VMs) was increased by infecting VMs with an adenovirus (Ad) containing a fusion gene encoding the β2a subunit of the LTCC (β2a)-GFP with AdGFP as the control (CTR). In vivo, we established transgenic mouse lines with inducible (Tet-off ) overexpression of the β2a subunit (β2a TG). All evaluations of mouse hearts or VMs were done with 4-month old mice. Results: Overexpression of β2a (MOI = 5) in cultured FVMs increased I Ca (111%) and cell volume (16%), protein synthesis (25%) and ANF expression; NFAT and HDAC translocations were increased in β2a FVMs (30% and 50% respectively); Blockade of the LTCC (nifedipine, NIF), intracellular Ca (BAPTA), calcineurin (cyclosporine A (CsA) and FK506) and CaMK II (KN93) prevented β2a mediated increases in cell volume, protein/DNA ratio, NFAT and HDAC translocations; The surface area of NRVMs infected with Adβ2a at 36 hours post infection was 52.4% larger than CTR, which was prevented by NIF, BAPTA, CsA, FK 506 and KN93; In TG mice, I Ca (CTR: 13.7 ± 0.7pA/pF, n=6 vs. TG: 24.3 ± 2.6pA/pF, n=6), fractional shortening (CTR: 8.0 ± 0.5%, n=16 vs. TG: 11.9 ± 1.1%, n=11) and peak Ca transient (Fluo-3) (CTR: 2.25 ± 0.08%, n=19 vs. TG: 3.37 ± 1.58, n=11) were significantly ( p 〈 0.05 ) increased in TG-VMs than in CTR-VMs; β2a TG mice had greater ejection fraction (CTR: 68.9 ± 1.3%, n=33 vs. TG: 74.4 ± 1.3%, n=34, p 〈 0.05), and posterior wall thickness (CTR: 1.10 ± 0.04mm, n=33 vs. TG: 1.22 ± 0.03mm, n=34, p 〈 0.001 ); The heart weight to body weight ratio in TG mice (6.90 ± 1.05mg/g, n=17) was greater ( p 〈 0.05 ) than in CTR (6.04 ± 0.93mg/g, n=51) with significantly larger myocyte cross-section area. Conclusion: Increases in Ca influx through the LTCC are sufficient to induce cardiomyocyte hypertrophy both in vitro and in vivo through the calcineurin/NFAT and HDAC dependent pathways.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.116.suppl_16.II_17-c
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
    detail.hit.zdb_id: 1466401-X
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  • 2
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    Adolescent Feline Heart Contains a Population of Small, Proliferative Ventricular Myocytes With Immature Physiological Properties
    Ovid Technologies (Wolters Kluwer Health) ; 2007
    In:  Circulation Research Vol. 100, No. 4 ( 2007-03-02), p. 536-544
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 100, No. 4 ( 2007-03-02), p. 536-544
    Abstract: Recent studies suggest that rather than being terminally differentiated, the adult heart is a self-renewing organ with the capacity to generate new myocytes from cardiac stem/progenitor cells (CS/PCs). This study examined the hypotheses that new myocytes are generated during adolescent growth, to increase myocyte number, and these newly formed myocytes are initially small, mononucleated, proliferation competent, and have immature properties. Ventricular myocytes (VMs) and cKit + (stem cell receptor) CS/PCs were isolated from 11- and 22-week feline hearts. Bromodeoxyuridine incorporation (in vivo) and p16 INK4a immunostaining were measured to assess myocyte cell cycle activity and senescence, respectively. Telomerase activity, contractions, Ca 2+ transients, and electrophysiology were compared in small mononucleated (SMMs) and large binucleated (LBMs) myocytes. Heart mass increased by 101% during adolescent growth, but left ventricular myocyte volume only increased by 77%. Most VMs were binucleated (87% versus 12% mononucleated) and larger than mononucleated myocytes. A greater percentage of SMMs was bromodeoxyuridine positive (SMMs versus LBMs: 3.1% versus 0.8%; P 〈 0.05), and p16 INK4a negative and small myocytes had greater telomerase activity than large myocytes. Contractions and Ca 2+ transients were prolonged in SMMs versus LBMs and Ca 2+ release was disorganized in SMMs with reduced transient outward current and T-tubule density. The T-type Ca 2+ current, usually seen in fetal/neonatal VMs, was found exclusively in SMMs and in myocytes derived from CS/PC. Myocyte number increases during adolescent cardiac growth. These new myocytes are initially small and functionally immature, with patterns of ion channel expression normally found in the fetal/neonatal period
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/01.RES.0000259560.39234.99
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
    detail.hit.zdb_id: 1467838-X
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  • 3
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    Acute Catecholamine Exposure Causes Reversible Myocyte Injury Without Cardiac Regeneration
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Circulation Research Vol. 119, No. 7 ( 2016-09-16), p. 865-879
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 119, No. 7 ( 2016-09-16), p. 865-879
    Abstract: Catecholamines increase cardiac contractility, but exposure to high concentrations or prolonged exposures can cause cardiac injury. A recent study demonstrated that a single subcutaneous injection of isoproterenol (ISO; 200 mg/kg) in mice causes acute myocyte death (8%–10%) with complete cardiac repair within a month. Cardiac regeneration was via endogenous cKit + cardiac stem cell–mediated new myocyte formation. Objective: Our goal was to validate this simple injury/regeneration system and use it to study the biology of newly forming adult cardiac myocytes. Methods and Results: C57BL/6 mice (n=173) were treated with single injections of vehicle, 200 or 300 mg/kg ISO, or 2 daily doses of 200 mg/kg ISO for 6 days. Echocardiography revealed transiently increased systolic function and unaltered diastolic function 1 day after single ISO injection. Single ISO injections also caused membrane injury in ≈10% of myocytes, but few of these myocytes appeared to be necrotic. Circulating troponin I levels after ISO were elevated, further documenting myocyte damage. However, myocyte apoptosis was not increased after ISO injury. Heart weight to body weight ratio and fibrosis were also not altered 28 days after ISO injection. Single- or multiple-dose ISO injury was not associated with an increase in the percentage of 5-ethynyl-2′-deoxyuridine–labeled myocytes. Furthermore, ISO injections did not increase new myocytes in cKit +/Cre ×R-GFP transgenic mice. Conclusions: A single dose of ISO causes injury in ≈10% of the cardiomyocytes. However, most of these myocytes seem to recover and do not elicit cKit + cardiac stem cell–derived myocyte regeneration.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/CIRCRESAHA.116.308687
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 1467838-X
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  • 4
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    Interaction of the Joining Region in Junctophilin-2 With the L-Type Ca 2+ Channel Is Pivotal for Cardiac Dyad Assembly and Intracellular Ca 2+ Dynamics
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation Research Vol. 128, No. 1 ( 2021-01-08), p. 92-114
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 128, No. 1 ( 2021-01-08), p. 92-114
    Abstract: Ca 2+ -induced Ca 2+ release (CICR) in normal hearts requires close approximation of L-type calcium channels (LTCCs) within the transverse tubules (T-tubules) and RyR (ryanodine receptors) within the junctional sarcoplasmic reticulum. CICR is disrupted in cardiac hypertrophy and heart failure, which is associated with loss of T-tubules and disruption of cardiac dyads. In these conditions, LTCCs are redistributed from the T-tubules to disrupt CICR. The molecular mechanism responsible for LTCCs recruitment to and from the T-tubules is not well known. JPH (junctophilin) 2 enables close association between T-tubules and the junctional sarcoplasmic reticulum to ensure efficient CICR. JPH2 has a so-called joining region that is located near domains that interact with T-tubular plasma membrane, where LTCCs are housed. The idea that this joining region directly interacts with LTCCs and contributes to LTCC recruitment to T-tubules is unknown. Objective: To determine if the joining region in JPH2 recruits LTCCs to T-tubules through direct molecular interaction in cardiomyocytes to enable efficient CICR. Methods and Results: Modified abundance of JPH2 and redistribution of LTCC were studied in left ventricular hypertrophy in vivo and in cultured adult feline and rat ventricular myocytes. Protein-protein interaction studies showed that the joining region in JPH2 interacts with LTCC-α1C subunit and causes LTCCs distribution to the dyads, where they colocalize with RyRs. A JPH2 with induced mutations in the joining region (mut PG1 JPH2) caused T-tubule remodeling and dyad loss, showing that an interaction between LTCC and JPH2 is crucial for T-tubule stabilization. mut PG1 JPH2 caused asynchronous Ca 2+ -release with impaired excitation-contraction coupling after β-adrenergic stimulation. The disturbed Ca 2+ regulation in mut PG1 JPH2 overexpressing myocytes caused calcium/calmodulin-dependent kinase II activation and altered myocyte bioenergetics. Conclusions: The interaction between LTCC and the joining region in JPH2 facilitates dyad assembly and maintains normal CICR in cardiomyocytes.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/CIRCRESAHA.119.315715
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467838-X
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  • 5
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    Abstract 8955: Cardiopulmonary Phenotyping of Sex-Based Differences in a Feline Model of HFpEF
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation Vol. 144, No. Suppl_1 ( 2021-11-16)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 144, No. Suppl_1 ( 2021-11-16)
    Abstract: Introduction: Approximately 50% of all heart failure (HF) diagnoses can be classified as HF with preserved ejection fraction (HFpEF), which has no FDA approved therapies. HFpEF is more prevalent in females compared to males, but the underlying mechanisms for the development as a sex-based disorder are unknown. We previously described how slow progressive pressure overload (PO) in male felines recapitulates the HFpEF phenotype but have not investigated the female phenotype. Hypothesis: Females will develop a less severe HFpEF phenotype compared to males under the same pathological stress. Methods & Results: Male (m) and female (f) domestic short felines (age 2mo) underwent aortic constriction (m: n=11; f: n=10) using a customized pre-shaped band or a sham procedure (m: n=7; f: n=7). Before surgery (baseline), there was no difference in body weight (BW) between groups and lung compliance was not different. Echocardiography revealed no significant difference in the ratio of left atrium to aortic root (LA/Ao), LA ejection fraction (LA EF), left ventricle (LV) ejection fraction, LV wall-thickness, and E/A ratio. By 4mo post-surgery, both males and females had developed cardiac dysfunction and decreased lung compliance. At this time, females had significantly smaller BWs than males. Despite the difference in BW, LV wall thickness and changes in E/A ratio were similar in both sexes in banded vs. shams. Importantly, LV EF did not change in any group. There was a decrease in LA EF and increased LA/Ao in all banded animals. Invasive hemodynamics at 4mo post-surgery showed no differences between sexes for the systolic pressure gradient generated by aortic banding. Banded males had higher LV end-diastolic pressure vs. banded females (m: 15.0±2.7mmHg; f: 8.1±1.9mmHg). However, there was a trend towards prolongation of tau and lower dp/dt min in banded females, suggestive of abnormal relaxation. There were no differences between banded males and females in heart weight/BW or cardiomyocyte cross-sectional area and both developed fibrosis. Conclusions: Exposure of male and female felines to PO resulted in similar cardiac hypertrophy, fibrosis, and decreased lung compliance. Females had lower LVEDP than males suggesting they may be protected from diastolic dysfunction.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.144.suppl_1.8955
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1466401-X
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  • 6
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    Alterations in Early Action Potential Repolarization Causes Localized Failure of Sarcoplasmic Reticulum Ca 2+ Release
    Ovid Technologies (Wolters Kluwer Health) ; 2005
    In:  Circulation Research Vol. 96, No. 5 ( 2005-03-18), p. 543-550
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 96, No. 5 ( 2005-03-18), p. 543-550
    Abstract: Depressed contractility of failing myocytes involves a decreased rate of rise of the Ca 2+ transient. Synchronization of Ca 2+ release from the junctional sarcoplasmic reticulum (SR) is responsible for the rapid rise of the normal Ca 2+ transient. This study examined the idea that spatially and temporally dyssynchronous SR Ca 2+ release slows the rise of the cytosolic Ca 2+ transient in failing feline myocytes. Left ventricular hypertrophy (LVH) with and without heart failure (HF) was induced in felines by constricting the ascending aorta. Ca 2+ transients were measured in ventricular myocytes using confocal line scan imaging. Ca 2+ transients were induced by field stimulation, square wave voltage steps, or action potential (AP) voltage clamp. SR Ca 2+ release was significantly less well spatially and temporally synchronized in field-stimulated HF versus control or LVH myocytes. Surprisingly, depolarization of HF cells to potentials where Ca 2+ currents ( I Ca ) were maximal resynchronized SR Ca 2+ release. Correspondingly, decreases in the amplitude of I Ca desynchronized SR Ca 2+ release in control, LVH, and HF myocytes to the same extent. HF myocytes had significant loss of phase 1 AP repolarization and smaller I Ca density, which should both reduce Ca 2+ influx. When normal myocytes were voltage clamped with HF AP profiles SR Ca 2+ release was desynchronized. SR Ca 2+ release becomes dyssynchronized in failing feline ventricular myocytes because of reductions in Ca 2+ influx induced in part by alterations in early repolarization of the AP. Therefore, therapies that restore normal early repolarization should improve the contractility of the failing heart.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/01.RES.0000158966.58380.37
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2005
    detail.hit.zdb_id: 1467838-X
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  • 7
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    Abstract 311: Single-Dose Isoproterenol does not Depress Cardiac Function in Mice
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Circulation Research Vol. 117, No. suppl_1 ( 2015-07-17)
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 117, No. suppl_1 ( 2015-07-17)
    Abstract: Rationale: Myocardial injury after repeated or continuous administration of isoproterenol (ISO) in preclinical models has been widely described in the literature by our lab and others. Recent controversial reports using a one-time dose of ISO, to mimic a Takotsubo-like cardiomyopathy, demonstrated pronounced and reversible depression of cardiac function at one-week post injection with widespread myocyte death followed by robust myocardial regeneration and recovery of cardiac function. Hypothesis: Single-dose ISO does not produce depression of cardiac function Methods and Results: C57Bl/6 mice were given a single subcutaneous injection of vehicle (saline) or 5, 200, or 300 mg/kg of ISO. Cardiac function was measured using transthoracic echocardiography with cardiac strain analysis at baseline prior to ISO injection and after 1, 7, 14, and 28 days post-injection. Animals were sacrificed after 1, 7, and 28 days post-injection for evaluation of gross heart weight (HW), HW/body weight (BW) and HW/tibia length (TL). Left ventricular (LV) functional measurements revealed no significant differences in global systolic function (ejection fraction and fractional shortening) between vehicle- or ISO-treated animals at any concentration. Additionally, no significant differences were detected between vehicle- or ISO-treated animals in any cardiac dimensions measured by echocardiography (LV cross-sectional area, internal diameter, end-diastolic or end-systolic volumes) or in gross HW, HW/BW or HW/TL. LV global cardiac strain was also not significantly different between vehicle and ISO-treated animals at any time point. When apical regions of the LV endocardium (the area most predominantly affected by Takotsubo cardiomyopathy) were specifically examined using strain analysis, no significant differences could be detected between vehicle and ISO-treated animals at any time point. Conclusion: Single-dose ISO injury in a mouse model does not produce any depression of cardiac function at 1 week post injection.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/res.117.suppl_1.311
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 1467838-X
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  • 8
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    Abstract 16434: Temporal Metabolomic and Transcriptomic Changes in a Large-Animal Model of Hfpef
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Vol. 142, No. Suppl_3 ( 2020-11-17)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. Suppl_3 ( 2020-11-17)
    Abstract: Heart failure with preserved ejection fraction (HFpEF) accounts for ~50% of HF cases, with no effective treatments. We previously reported that a feline aortic banding model recapitulates many of the multi-factorial features of HFpEF, including: LV hypertrophy, left atrial enlargement, elevated LV filling pressures, impaired pulmonary mechanics and fibrosis. Importantly, this model lacks obesity and hypertension enabling the discovery of cardiac centric targets independent of comorbidities. We examined early changes in metabolism and transcription to gain mechanistic insight into HFpEF development. Male short-hair kittens (2mo old) underwent aortic banding or sham operation. Cardiac function was assessed at baseline and 1mo post-banding prior to tissue collection and downstream analyses. Following banding, we observed significant cardiac hypertrophy and initiation of LV fibrosis in the absence of changes in cardiac function. We observed LV mitochondrial dysfunction, indicated by impaired complex-I and -II respiration prompting the examination of cardiac metabolism by unbiased metabolomics. 82 metabolites were significantly different (≥ 1.25 fold, p ≤ 0.1) between 1mo banded and sham hearts, with an overrepresentation of amino acid (aa) and lipid species. Pathway enrichment analysis highlighted an increase in aa metabolism (e.g. serine, proline) that is associated with ECM remodeling and tissue fibrosis. Additionally, an increase in lipid species (i.e. acyl-carnitines) suggests reduced fatty acid utilization and a shift towards glycolysis. Correlations of metabolomics data with mitochondrial function and cardiac phenotyping revealed strong associations between mitochondrial function and the cardiac energy state, as well as aa and LV fibrosis. RNA-seq and enrichment analyses revealed a significant inflammatory response early in disease progression and a decrease in protein/histone acetylation. Collectively, this systems-based approach provides new insights into the cellular biology underlying HFpEF-like disease progression. The metabolic and transcriptional signature that precede the clinical features of HFpEF, will provide new pre-clinical research directions and may yield novel therapeutic targets.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.142.suppl_3.16434
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1466401-X
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  • 9
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    Unique Features of Cortical Bone Stem Cells Associated With Repair of the Injured Heart
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Circulation Research Vol. 117, No. 12 ( 2015-12-04), p. 1024-1033
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 117, No. 12 ( 2015-12-04), p. 1024-1033
    Abstract: Adoptive transfer of multiple stem cell types has only had modest effects on the structure and function of failing human hearts. Despite increasing the use of stem cell therapies, consensus on the optimal stem cell type is not adequately defined. The modest cardiac repair and functional improvement in patients with cardiac disease warrants identification of a novel stem cell population that possesses properties that induce a more substantial improvement in patients with heart failure. Objective: To characterize and compare surface marker expression, proliferation, survival, migration, and differentiation capacity of cortical bone stem cells (CBSCs) relative to mesenchymal stem cells (MSCs) and cardiac-derived stem cells (CDCs), which have already been tested in early stage clinical trials. Methods and Results: CBSCs, MSCs, and CDCs were isolated from Gottingen miniswine or transgenic C57/BL6 mice expressing enhanced green fluorescent protein and were expanded in vitro. CBSCs possess a unique surface marker profile, including high expression of CD61 and integrin β4 versus CDCs and MSCs. In addition, CBSCs were morphologically distinct and showed enhanced proliferation capacity versus CDCs and MSCs. CBSCs had significantly better survival after exposure to an apoptotic stimuli when compared with MSCs. ATP and histamine induced a transient increase of intracellular Ca 2+ concentration in CBSCs versus CDCs and MSCs, which either respond to ATP or histamine only further documenting the differences between the 3 cell types. Conclusions: CBSCs are unique from CDCs and MSCs and possess enhanced proliferative, survival, and lineage commitment capacity that could account for the enhanced protective effects after cardiac injury.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/CIRCRESAHA.115.307362
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 1467838-X
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  • 10
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    Abstract 53: Characterization of a Feline HFpEF Model Induced by Slow Progressive Pressure Overload
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Circulation Research Vol. 119, No. suppl_1 ( 2016-07-22)
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 119, No. suppl_1 ( 2016-07-22)
    Abstract: Rationale: The prevalence of Heart Failure with preserved Ejection Fraction (HFpEF) is almost equal to that of Heart Failure with reduced Ejection Fraction (HFrEF) and represents a major public health problem. There are no proven effective treatments for HFpEF, partially attributable to the lack of well-established animal models for HFpEF. Hypothesis: Cats develop a HFpEF phenotype similar to patients after induction of slow progressive pressure overload. Methods and Results: Female and male short hair cats, aged 2 months, underwent either aortic constriction, with a customized pre-shaped band, or sham procedure. In contrast to immediate pressure overload, this approach results in a slow progressive pressure overload during growth. Transthoracic echocardiography was performed at baseline and 1, 2, 3, and 4 months after banding. Concentric LV hypertrophy was observed and heart weight to body weight ratio significantly increased in banded male and female cats compared to sham (male: 8.5±1.6 vs. 4.5±0.4; female: 7.4±0.2 vs. 4.9±0.8; p 〈 0.05). Wet/dry lung weight ratio, indicating pulmonary congestion, did not differ between groups. End-diastolic wall thickness was significantly increased in banded cats at 2, 3 and 4 months, while the end-diastolic diameter and systolic function did not differ between banded and sham cats at any time point. A significant left atrial (LA) enlargement was observed in banded cats at 3 and 4 months, as measured by an increased LA/aorta ratio and increased LA area. LA ejection fraction was significantly decreased after aortic constriction (male sham vs. banded: 75.4±0.2 vs. 47.3±0.2; p 〈 0.01; female sham vs. band: 75.4±2.1 vs. 53.9±4.4; p 〈 0.05). Diastolic function, assessed by tissue Doppler imaging, was impaired in banded cats. Summary and Conclusion: Slow progressive pressure overload in cats induces severe LV concentric hypertrophy, LA enlargement and dysfunction without causing LV dilation or systolic dysfunction, mimicking many clinical phenotypes in HFpEF patients. Further characterization will include incorporating invasive measurements, exercise capacity and serum biomarkers and testing of novel therapies.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/res.119.suppl_1.53
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 1467838-X
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