Role of Amino Acids and Genetic Disorder in Pathogenesis of Heart Failure

January 8, 2019 updated by: Reham I El-mahdy, Assiut University
Heart failure (HF) is a continuously growing public health problem. The study aim to provide novel insights into the role of amino acids in pathogenesis of heart failure, to obtain a better understanding of cardiac ryanodine Receptor 2 role as an essential player in excitation-contraction coupling in pathogenesis of heart failure and clarify the potential value of these markers as targets for heart failure therapy

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Heart failure (HF) is a continuously growing public health problem. Presently, almost 40 million people are affected by heart failure worldwide. According to World Health Organization (WHO), cardiovascular diseases are number one cause of deaths globally . In developed countries, the prevalence of heart failure is approximately 1-2% of the adult population. In Egypt, the prevalence of HF with preserved ejection fraction represents about 34.2 % while heart failure with reduced ejection fraction represents 65.8 % of total heart failure cases .

A broad range of cardiac diseases, inherited disorders, and systematic diseases can result in heart failure. The situation is even more complex, as heart failure can have mixed etiologies. Heart failure itself represents a final common pathway in response to genetic and/or environmental influences. A clear genetic identification can positively influence patient treatment and, thereby, improve prognosis. Besides, understanding the pathogenesis of genetically induced heart failure at it molecular level may lead to the development of specific individual heart failure therapies in the future.

The human heart uses large amounts of amino acids (AAs) as regulators of both myocardium protein turnover and energy metabolism, but uses few AAs as substrates for direct energy production .The heart's reliance on AAs increases during heart failure because of high myocardium anabolic activity and cardiomyocyte energy shortage. Anabolic activity of the ventricle wall is induced by both high levels of ventricular pressure and a myocardial substrate shift from fatty acid oxidation (FAOX) to glucose oxidation (GLUOX).

Various mechanisms may potentially be operating during CHF to impair arterial AAs, including inadequate protein-energy intake, body AA overconsumption, particularly in hyper metabolic states, increased remodeling activity of the heart and lung and finally, the development of pathogenic gut flora. Understanding arterial AA levels could be useful to understand whether heart anabolic activity and remaining heart capacity of energy production are being threatened by low AA s and furthermore may allow us to correct altered AAs through diet and/or supplementation of specific free AAs.

A reduction in essential AAs in CHF subjects, shows the disease severity-related decline of arterial levels of those non-essential (and essential methionine) AAs with the greatest impact on myocardium energetics, anti-oxidative capacity and myocardial protein remodeling.

Calcium cycling protein and heart failure Ca2+-dependent signaling is highly regulated in cardiomyocytes and determines the force of cardiac muscle contraction. Ca2+ cycling refers to the release and reuptake of intracellular Ca2+ that drives muscle contraction and relaxation in failing hearts. Ca2+ cycling is profoundly altered, resulting in impaired contractility and fatal cardiac arrhythmias. The key defects in Ca2+ cycling occur at the level of the sarcoplasmic reticulum (SR), a Ca2+ storage organelle in muscle. Defects in the regulation of Ca2+ cycling proteins including the ryanodine receptor 2 (RyR2) a cardiac Ca2+ release channel macromolecular complexes and the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase2a (SERCA2a) contribute to heart failure.

Phosphorylation of the cardiac ryanodine receptor (RyR2) phospho-site S2808 has hallmark of heart failure (HF) and a critical mediator of the physiological fight or flight response of the heart. In support of this hypothesis, mice unable to undergo phosphorylation at RyR2-S2808 (S2808A) were significantly protected against HF and displayed a blunted response to adrenergic stimulation.

Study Type

Observational

Enrollment (Anticipated)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Heart failure patients

Description

Inclusion Criteria:

• According to American Heart Association, patients with manifestation of heart failure (dyspnea, edema in the feet, ankles, legs or abdomen, heart palpitations) as diagnosed by clinical examination, laboratory investigations and imaging techniques.

Exclusion Criteria:

  • Diabetic patients
  • Neurological disorders
  • Cancers.
  • Obese patient
  • Smokers
  • Patient with chest infection

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Group I:
Thirty heart failure patients
Genetic: Ryanodine Receptor 2 gene expression
Ryanodine Receptor 2 gene expression will be measured by real time PCR. In addition, amino acids analysis will be measured in plasma by amino acid analyzer.
Group II:
Twenty healthy controls
Genetic: Ryanodine Receptor 2 gene expression
Ryanodine Receptor 2 gene expression will be measured by real time PCR. In addition, amino acids analysis will be measured in plasma by amino acid analyzer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Decrease cardiac ryanodine Receptor 2 gene expression and change of amino acids levels in patients with heart failure.
Time Frame: Baseline
better understanding of cardiac ryanodine Receptor 2 role as an essential player in excitation-contraction coupling in pathogenesis of heart failure and the role of amino acids in pathogenesis of heart failure
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

January 17, 2019

Primary Completion (ANTICIPATED)

March 28, 2019

Study Completion (ANTICIPATED)

March 30, 2019

Study Registration Dates

First Submitted

July 7, 2018

First Submitted That Met QC Criteria

July 7, 2018

First Posted (ACTUAL)

July 18, 2018

Study Record Updates

Last Update Posted (ACTUAL)

January 9, 2019

Last Update Submitted That Met QC Criteria

January 8, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Heart failure

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Heart Failure

Clinical Trials on Ryanodine Receptor 2 gene expression

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Taiwan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe