P5998The Phosphodiesterase 4D interacting protein averts volume overload - but not pressure overload-induced pathological myocardial remodeling

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
B A Mohamed ◽  
M Elkenani ◽  
J Jakubiczka-Smorag ◽  
M Bader ◽  
G Hasenfuss ◽  
...  
Keyword(s):  
Pressure Overload ◽  
Mortality Rates ◽  
Structure And Function ◽  
Cardiac Structure ◽  
Myocardial Remodeling ◽  
Interacting Protein ◽  
Protein Levels ◽  
Cardiac Structure And Function ◽  
And Function ◽  
Phosphodiesterase 4D

Abstract Background Although volume- and pressure-overload (VO and PO, respectively) are hemodynamic stress, each results in distinct phenotypes. The Phosphodiesterase 4D interacting protein (PDE4DIP) is a protein involved in cardiac muscle contraction and suggested to play a role in cardiomyopathy. We previously identified Pde4dip transcript as being downregulated in VO but upregulated in PO. Objective We wanted to address whether Pde4dip deletion would alter the progression of pathological myocardial remodeling and heart failure (HF) following hemodynamic stress. Methods Pde4dip knockout (Pde4dip-KO) and age- and sex-matched wild-type (WT) mice were exposed to aortocaval shunt-triggered VO or transthoracic aortic constriction (TAC)-induced PO. Mortality rates were assessed and the cardiac structure and function were determined by serial echocardiography. Results The PDE4DIP protein levels decreased significantly in volume-overloaded hearts. However, pressure-overloaded hearts did not alter PDE4DIP protein levels, suggesting different posttranscriptional modifications that might affect the PDE4DIP protein expression in VO versus PO. The Pde4dip-KO Hearts were structurally and functionally normal in echocardiographic and morphometric analyses. However, Pde4dip deletion mildly attenuated the mortality rates in shunt-, but not in TAC-operated mice. A significant deterioration of left ventricle geometry and function was observed in volume-overloaded WT hearts at 12 weeks after shunt, but preserved cardiac function were noticed in shunt-operated Pde4dip-KO mice. On the other hand, TAC-operated WT and Pde4dip-KO mice exhibited a significant, but comparable deterioration of cardiac structure and function compared to sham mice. Conclusion Here we identified the PDE4DIP as an essential regulator of pathological myocardial remodeling following VO, but irrelevant to the development of cardiac dysfunction after TAC. Further investigations are warranted to dissect the possible mechanisms underlying the protective role of PDE4DIP deletion in the setting of VO. Acknowledgement/Funding This work was supported by DFG (SFB1002 project D04 to KT and D01 to GH; IRTG1816 to ME); BAM was funded by DSHF

scholarly journals Omega-3 fatty acid prevents the development of heart failure by changing fatty acid composition in the heart

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Haruhiro Toko ◽  
Hiroyuki Morita ◽  
Masanori Katakura ◽  
Michio Hashimoto ◽  
Toshiyuki Ko ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Pressure Overload ◽  
Structure And Function ◽  
Free Form ◽  
Cardiac Structure ◽  
Omega 3 ◽  
Omega 3 Fatty Acid ◽  
Beneficial Effects ◽  
Cardiac Structure And Function ◽  
And Function

Abstract Some clinical trials showed that omega-3 fatty acid (FA) reduced cardiovascular events, but it remains unknown whether omega-3 FA supplementation changes the composition of FAs and their metabolites in the heart and how the changes, if any, exert beneficial effects on cardiac structure and function. To clarify these issues, we supplied omega-3 FA to mice exposed to pressure overload, and examined cardiac structure and function by echocardiography and a proportion of FAs and their metabolites by gas chromatography and liquid chromatography-tandem mass spectrometry, respectively. Pressure overload induced cardiac hypertrophy and dysfunction, and reduced concentration of all FAs’ components and increased free form arachidonic acid and its metabolites, precursors of pro-inflammatory mediators in the heart. Omega-3 FA supplementation increased both total and free form of eicosapentaenoic acid, a precursor of pro-resolution mediators and reduced free form arachidonic acid in the heart. Omega-3 FA supplementation suppressed expressions of pro-inflammatory cytokines and the infiltration of inflammatory cells into the heart and ameliorated cardiac dysfunction and fibrosis. These results suggest that omega-3 FA-induced changes of FAs composition in the heart have beneficial effects on cardiac function via regulating inflammation.

Cardiac-specific attenuation of natriuretic peptide A receptor activity accentuates adverse cardiac remodeling and mortality in response to pressure overload

2005 ◽  
Vol 289 (2) ◽  
pp. H777-H784 ◽  
Author(s):  
Jeetendra B. Patel ◽  
Maria L. Valencik ◽  
Allison M. Pritchett ◽  
John C. Burnett ◽  
John A. McDonald ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Pressure Overload ◽  
Structure And Function ◽  
The Body ◽  
Cardiac Structure ◽  
Paracrine Effects ◽  
Cardiac Structure And Function ◽  
And Function

Atrial (ANP) and brain (BNP) natriuretic peptides are hormones of myocardial cell origin. These hormones bind to the natriuretic peptide A receptor (NPRA) throughout the body, stimulating cGMP production and playing a key role in blood pressure control. Because NPRA receptors are present on cardiomyocytes, we hypothesized that natriuretic peptides may have direct autocrine or paracrine effects on cardiomyocytes or adjacent cardiac cells. Because both natriuretic peptides and NPRA gene expression are upregulated in states of pressure overload, we speculated that the effects of the natriuretic peptides on cardiac structure and function would be most apparent after pressure overload. To attenuate cardiomyocyte NPRA activity, transgenic mice with cardiac specific expression of a dominant-negative (DN-NPRA) mutation (HCAT D 893A) in the NPRA receptor were created. Cardiac structure and function were assessed (avertin anesthesia) in the absence and presence of pressure overload produced by suprarenal aortic banding. In the absence of pressure overload, basal and BNP-stimulated guanylyl cyclase activity assessed in cardiac membrane fractions was reduced. However, systolic blood pressure, myocardial cGMP, log plasma ANP levels, and ventricular structure and function were similar in wild-type (WT-NPRA) and DN-NPRA mice. In the presence of pressure overload, myocardial cGMP levels were reduced, and ventricular hypertrophy, fibrosis, filling pressures, and mortality were increased in DN-NPRA compared with WT-NPRA mice. In addition to their hormonal effects, endogenous natriuretic peptides exert physiologically relevant autocrine and paracrine effects via cardiomyocyte NPRA receptors to modulate cardiac hypertrophy and fibrosis in response to pressure overload.

scholarly journals Impact of the severity of end-stage liver disease in cardiac structure and function

2013 ◽  
Vol 12 (1) ◽  
pp. 85-91 ◽  
Author(s):  
Odilson Marcos Silvestre ◽  
Fernando Bacal ◽  
Danusa de Souza Ramos ◽  
Jose L. Andrade ◽  
Meive Furtado ◽  
...  
Keyword(s):  
Liver Disease ◽  
Structure And Function ◽  
Cardiac Structure ◽  
End Stage Liver Disease ◽  
Cardiac Structure And Function ◽  
End Stage ◽  
And Function

scholarly journals Development of a semi-automated segmentation tool for high frequency ultrasound image analysis of mouse echocardiograms

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kristi Powers ◽  
Raymond Chang ◽  
Justin Torello ◽  
Rhonda Silva ◽  
Yannick Cadoret ◽  
...  
Keyword(s):  
Image Analysis ◽  
Automated Analysis ◽  
Structure And Function ◽  
Ultrasound Images ◽  
Cardiac Structure ◽  
Short Axis ◽  
Pixel Intensity ◽  
Cardiac Structure And Function ◽  
And Function

AbstractEchocardiography is a widely used and clinically translatable imaging modality for the evaluation of cardiac structure and function in preclinical drug discovery and development. Echocardiograms are among the first in vivo diagnostic tools utilized to evaluate the heart due to its relatively low cost, high throughput acquisition, and non-invasive nature; however lengthy manual image analysis, intra- and inter-operator variability, and subjective image analysis presents a challenge for reproducible data generation in preclinical research. To combat the image-processing bottleneck and address both variability and reproducibly challenges, we developed a semi-automated analysis algorithm workflow to analyze long- and short-axis murine left ventricle (LV) ultrasound images. The long-axis B-mode algorithm executes a script protocol that is trained using a reference library of 322 manually segmented LV ultrasound images. The short-axis script was engineered to analyze M-mode ultrasound images in a semi-automated fashion using a pixel intensity evaluation approach, allowing analysts to place two seed-points to triangulate the local maxima of LV wall boundary annotations. Blinded operator evaluation of the semi-automated analysis tool was performed and compared to the current manual segmentation methodology for testing inter- and intra-operator reproducibility at baseline and after a pharmacologic challenge. Comparisons between manual and semi-automatic derivation of LV ejection fraction resulted in a relative difference of 1% for long-axis (B-mode) images and 2.7% for short-axis (M-mode) images. Our semi-automatic workflow approach reduces image analysis time and subjective bias, as well as decreases inter- and intra-operator variability, thereby enhancing throughput and improving data quality for pre-clinical in vivo studies that incorporate cardiac structure and function endpoints.

scholarly journals The mitral regurgitation effects of cardiac structure and function in left ventricular noncompaction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Qing Zou ◽  
Rong Xu ◽  
Xiao Li ◽  
Hua-yan Xu ◽  
Zhi-gang Yang ◽  
...  
Keyword(s):  
Mitral Regurgitation ◽  
Nyha Class ◽  
Left Ventricular ◽  
Structure And Function ◽  
Left Ventricular Geometry ◽  
Cardiac Structure ◽  
Left Ventricular Noncompaction ◽  
Ventricular Noncompaction ◽  
Cardiac Structure And Function ◽  
And Function

AbstractThis study evaluated the effects of mitral regurgitation (MR) on cardiac structure and function in left ventricular noncompaction (LVNC) patients. The clinical and cardiovascular magnetic resonance (CMR) data for 182 patients with noncompaction or hypertrabeculation from three institutes were retrospectively included. We analyzed the difference in left ventricular geometry, cardiac function between LVNC patients with and without MR. The results showed that patients with MR had a worse New York Heart Association (NYHA) class and a higher incidence of arrhythmia (P < 0.05). MR occurred in 48.2% of LVNC patients. Compared to LVNC patients without MR, the two-dimensional sphericity index, maximum/minimum end-diastolic ratio and longitudinal shortening in LVNC patients with MR were lower (P < 0.05), and the peak longitudinal strain (PLS) of the global and segmental myocardium were obviously reduced (P < 0.05). No significant difference was found in strain in LVNC patients with different degree of MR; end diastolic volume, end systolic volume, and global PLS were statistically associated with MR and NYHA class (P < 0.05), but the non-compacted to compacted myocardium ratio had no significant correlation with them. In conclusion, the presence of MR is common in LVNC patients. LVNC patients with MR feature more severe morphological and functional changes. Hypertrabeculation is not an important factor affecting structure and function at the heart failure stage.

scholarly journals Differences between diabetic and non-diabetic nephropathy patients in cardiac structure and function at the beginning of hemodialysis and their impact on the prediction of mortality

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199758
Author(s):  
Chao Tang ◽  
Han Ouyang ◽  
Jian Huang ◽  
Jing Zhu ◽  
Xiaosong Gu
Keyword(s):  
Diabetic Nephropathy ◽  
Diastolic Dysfunction ◽  
Peak Velocity ◽  
Structure And Function ◽  
Cardiac Valve ◽  
Cardiac Structure ◽  
Prediction Of Mortality ◽  
Cardiac Structure And Function ◽  
Lv Diastolic Dysfunction ◽  
And Function

Objectives To characterize differences in cardiac structure and function in hemodialysis (HD) patients with diabetic nephropathy (DN) and in those without using echocardiography and to determine their impact on the prediction of mortality using echocardiographic parameters. Methods Clinical, laboratory, and echocardiographic data were collected from patients commencing HD. Results Compared with those without DN, patients with DN had lower peak velocity of the early diastolic wave (e′), larger left atria, and higher peak early diastolic velocity (E)/e′ and peak velocity of tricuspid regurgitation (TR). In addition, a larger proportion of DN patients had a combination of left ventricular (LV) diastolic dysfunction, cardiac valve calcification, moderate-to-severe cardiac valve regurgitation (CVR), and at least moderate pericardial effusion (PE). After accounting for age, sex, smoking, hypertension, hemoglobin, and albumin, DN was responsible for e′  < 10 cm/s, E/e′ >13 m/s, TR >2.8 m/s, LV diastolic dysfunction, CVR, and PE. LV diastolic dysfunction and E/e′ >13 were the most useful predictors of mortality in patients with DN. Conclusions Patients with DN who undergo HD tend to have worse LV diastolic function and are more likely to have heart valve problems. LV diastolic dysfunction and E/e′ are predictors of death in DN patients.

scholarly journals Smoking and Cardiac Structure and Function in the Elderly

2016 ◽  
Vol 9 (9) ◽  
Author(s):  
Wilson Nadruz ◽  
Brian Claggett ◽  
Alexandra Gonçalves ◽  
Gabriela Querejeta-Roca ◽  
Miguel M. Fernandes-Silva ◽  
...  
Keyword(s):  
The Elderly ◽  
Structure And Function ◽  
Cardiac Structure ◽  
Cardiac Structure And Function ◽  
And Function
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