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Dataset results
233 results for “Diastole”
The Ubiquitin Ligase WWP1 Contributes to Shifts in Matrix Proteolytic Profiles and a Myocardial Aging Phenotype with Diastolic Heart Failure
<p><strong><em>Aims</em></strong>. Ubiquitylation is a key event that regulates protein turnover, and induction of the ubiquitin ligase E3 WWP1 has been associated with age. Left ventricular hypertrophy (LVH) commonly occurs as a function of age and can cause heart failure with a preserved ejection fraction (EF; HFpEF). We hypothesized that overexpression (O/E) of WWP1 in the heart would cause LVH as well as functional and structural changes consistent with the aging HFpEF phenotype.</p> <p><strong><em>Methods and Results.</em></strong> Global WWP1 O/E was achieved in mice (n=11) and echocardiography (40 MHz) performed to measure LV mass, EF, Doppler velocities (early-E, late/atrial-A), myocardial relaxation (E’), and isovolumetric relaxation time (IVRT) at 4, 6, and 8 weeks. Age matched wild type animals (n=15) were included as referent controls. LV EF was identical (60+1% vs 60+1%, p>0.90) with no difference in LV mass (67+3 vs 75+5, p>0.25) at 4 weeks. However, at 8 weeks of age, LV mass increased by over two-fold, E/A fell (impaired passive filling), and E/E’ was lower and IVRT prolonged (impaired LV relaxation) - all p<0.05. Collagen percent area increased by over two-fold and fibrillar collagen expression (rtPCR) by over 1.5 fold (p<0.05) with WWP1 O/E. WWP1 with an anti-WWP1 antibody could be identified in isolated cardiac fibroblasts with WWP1 increased by over two-fold in O/E fibroblasts (p<0.05).</p> <p><strong><em>Conclusion.</em></strong> Inducing WWP1 expression caused LVH, preserved systolic function, but impaired diastolic dysfunction, consistent with the HFpEF phenotype. Targeting the WWP1 pathway may be a novel therapeutic target for this intractable form of HF associated with aging.</p>
The Ubiquitin Ligase WWP1 Contributes to Shifts in Matrix Proteolytic Profiles and a Myocardial Ageing Phenotype with Diastolic Heart Failure
<p><strong><em>Aims</em></strong>. Ubiquitylation is a key event that regulates protein turnover, and induction of the ubiquitin ligase E3 WWP1 has been associated with age. Left ventricular hypertrophy (LVH) commonly occurs as a function of age and can cause heart failure with a preserved ejection fraction (EF; HFpEF). We hypothesized that overexpression (O/E) of WWP1 in the heart would cause LVH as well as functional and structural changes consistent with the ageing HFpEF phenotype.</p> <p><strong><em>Methods and Results.</em></strong> Global WWP1 O/E was achieved in mice (n=11) and echocardiography (40 MHz) performed to measure LV mass, EF, Doppler velocities (early-E, late/atrial-A), myocardial relaxation (E’), and isovolumetric relaxation time (IVRT) at 4, 6, and 8 weeks. Age matched wild type animals (n=15) were included as referent controls. LV EF was identical (60+1% vs 60+1%, p>0.90) with no difference in LV mass (67+3 vs 75+5, p>0.25) at 4 weeks. LVH and diastolic dysfunction occurred with WWP1 O/E wherein LV mass increased by over two-fold, E/A fell (impaired passive filling), and E/E’ was lower and IVRT prolonged (impaired LV relaxation). Collagen percent area increased by over two-fold with WWP1 O/E and increased expression of determinants of fibrosis and growth (qPCR) were also concomitantly increased.</p> <p><strong><em>Conclusion.</em></strong> Inducing WWP1 expression caused LVH with significant diastolic dysfunction, consistent with the HFpEF phenotype. Thus, targeting the WWP1 pathway may be a novel therapeutic target for this intractable form of HF associated with ageing</p>
Noninvasive Neuromodulation to Reserve Diastolic Dysfunction
ClinicalTrials.gov study NCT02983448. IPD Sharing: UNDECIDED. Countries: 1. Publications: 1.
CoQ10 and D-ribose in Patients With Diastolic Heart Failure
ClinicalTrials.gov study NCT03133793. IPD Sharing: NO. Countries: 1. Publications: 2.
Effects of Nebivolol on Exercise Tolerance and Left Ventricular Systolic and Diastolic Function
ClinicalTrials.gov study NCT01056718. IPD Sharing: NO. Countries: 1. Publications: 1.
Improving Metabolic Health in Patients With Diastolic Dysfunction
ClinicalTrials.gov study NCT03448185. IPD Sharing: NO. Countries: 1. Publications: 1.
Randomized Clinical Trial: Expectant Management vs Laser Treatment of Monochorionic Twins With Severe Selective Intrauterine Growth Retardation and Absent or Reverse Diastolic Flow in the Umbilical Ar
ClinicalTrials.gov study NCT01177553. IPD Sharing: Not stated. Countries: 1. Publications: 32.
Effect of Intradialytic Exercise on Left Ventricular Diastolic Function in Hemodialysis Patients
ClinicalTrials.gov study NCT06584734. IPD Sharing: NO. Countries: 1. Publications: 33.
Effects of the Dietary Approaches to Stop Hypertension(DASH) Sodium-restricted Diet in Diastolic Heart Failure
ClinicalTrials.gov study NCT00939640. IPD Sharing: Not stated. Countries: 1. Publications: 11.
A Study of the Effectiveness of Sitaxsentan Sodium in Patients With Diastolic Heart Failure
ClinicalTrials.gov study NCT00303498. IPD Sharing: YES. Countries: 2. Publications: 1.
Evaluating the Effectiveness of Sildenafil at Improving Health Outcomes and Exercise Ability in People With Diastolic Heart Failure (The RELAX Study)
ClinicalTrials.gov study NCT00763867. IPD Sharing: Not stated. Countries: 2. Publications: 13.
The Effects of Systolic Blood Pressure Lowering on Diastolic Function Using Valsartan + Amlodipine in Patients With Hypertension and Diastolic Dysfunction
ClinicalTrials.gov study NCT00523549. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Study to Determine How Cialis Effects the Renal Function in Response to Volume Expansion in Preclinical Diastolic Cardiomyopathy (Aim3)
ClinicalTrials.gov study NCT02058095. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Exercise Intolerance in Elderly Patients With Diastolic Heart Failure
ClinicalTrials.gov study NCT00959660. IPD Sharing: Not stated. Countries: 1. Publications: 5.
High Intensity Interval Exercise in Diastolic Heart Failure
ClinicalTrials.gov study NCT02147613. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Ubiquitin Ligase Wwp1 Gene Deletion Attenuates Diastolic Dysfunction in Pressure Overload Hypertrophy
<p><strong><em>Background.</em></strong> Heart failure with a preserved left ventricular (LV) ejection fraction (HFpEF) often arises from a prolonged LV pressure overload (LVPO) and accompanied by abnormal extracellular matrix (ECM) accumulation. The E3 ubiquitin ligase WWP1 is a fundamental determinant ECM turnover. We tested the hypothesis that genetic ablation of<em> Wwp1</em> would alter the progression of LVPO induced HFpEF.</p> <p><strong><em>Methods/Results</em></strong><em>.</em> LV echocardiography in mice with global <em>Wwp1</em> deletion (n=41; <em>Wwp1<sup>-/-</sup></em>) was performed at 12 weeks of age (Baseline) and then at 2 and 4 weeks following LVPO (transverse aortic banding) or surgery without LVPO induction. Age-matched wild type mice (<em>Wwp1<sup>+/+</sup></em>; n=33) underwent identical protocols. LV EF remained constant and unchanged with LVPO and LV mass increased in both groups but was lower in the <em>Wwp1<sup>-/-</sup></em> mice. With LVPO, the E/A ratio, an index of LV filling, was 3.97 + 0.46 in <em>Wwp1<sup>+/+</sup></em> but was 1.73 + 0.19 in the <em>Wwp1<sup>-/-</sup></em> group (p<0.05). At the transcriptional level, mRNA for fibrillar collagens (types I and III) decreased by approximately 50% in <em>Wwp1<sup>-/-</sup></em> compared to the <em>Wwp1<sup>+/+</sup></em> group at 4 weeks post-LVPO (p<0.05) and was paralleled by a similar difference in LV fibrillar collagen content as measured by histochemistry. Moreover, mRNA levels for determinants favoring ECM accumulation, such as transforming growth factor (TGF) increased with LVPO, but were lower in the <em>Wwp1<sup>-/-</sup></em> group.</p> <p><strong><em>Summary.</em></strong> The absence of <em>Wwp1</em> reduced the development of LVH and subsequent progression to HFpEF. Modulating the WWP1 pathway could be a therapeutic target to alter the natural history of HFpEF.</p>
Safety and Efficacy of Bosentan in Patients With Diastolic Heart Failure and Secondary Pulmonary Hypertension
ClinicalTrials.gov study NCT00820352. IPD Sharing: Not stated. Countries: 1. Publications: 20.
Effects of Remifentanil on Cardiac Function in Patients With Diastolic Dysfunction
ClinicalTrials.gov study NCT04117009. IPD Sharing: NO. Countries: 1. Publications: 2.
AlEX-DHF: Ablation and Exercise in Diastolic Heart Failure
ClinicalTrials.gov study NCT06650995. IPD Sharing: NO. Countries: 1. Publications: 9.
The Effect of Exercise and Alagebrium on the Diastolic Function of the Heart
ClinicalTrials.gov study NCT01014572. IPD Sharing: Not stated. Countries: 1. Publications: 1.
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