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Related Concept Videos

Imbalances in Cardiac Output01:26

Imbalances in Cardiac Output

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The heart's primary function is to pump blood throughout the body, maintaining a balance between blood sent out (cardiac output) and blood returning (venous return). If this balance is disrupted, it can result in congestive heart failure (CHF), a severe condition where the heart becomes an inefficient pump, leading to inadequate blood circulation.
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Pathophysiology of Cardiac Performance01:29

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Typical heart performance is influenced by heart rate, rhythm, myocardial contraction, and metabolism or blood flow. The cardiac muscle exhibits distinct electrophysiological features, including pacemaker activity and calcium channel control, which play a vital role in the heart's response to various drugs. The autonomic nervous system, comprising the sympathetic and parasympathetic branches, regulates heart rate. Sympathetic activation increases heart rate, while parasympathetic activation...
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Cardiomyopathy IV: Restrictive Cardiomyopathy01:29

Cardiomyopathy IV: Restrictive Cardiomyopathy

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Restrictive cardiomyopathy (RCM) is a rare heart muscle disease characterized by impaired ventricular filling due to stiffened ventricular walls, leading to significant diastolic dysfunction.EtiologyRestrictive cardiomyopathy can arise from both inherited and acquired diseases, many of which are systemic. It is categorized into four main types: infiltrative, storage, non-infiltrative, and endomyocardial diseases.Infiltrative diseases, such as amyloidosis, lead to RCM by depositing amyloid...
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Pathophysiology of Heart Failure01:17

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Heart failure (HF) is a progressive syndrome involving ventricles that leads to inadequate cardiac output. It can be classified based on location and output or ejection fraction. Ejection fraction (EF) is an essential measurement in the diagnosis and surveillance of HF. Reduced EF corresponds to systolic heart failure (HFrEF). However, HF with preserved ejection fraction (HFpEF) is becoming increasingly prevalent. Also known as diastolic HF, this form of HF is related to aging. The...
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Heart Failure I: Introduction01:27

Heart Failure I: Introduction

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Heart failure refers to a clinical syndrome caused by structural or functional cardiac disorders that prevent the heart from pumping an adequate amount of blood to meet the body's metabolic needs. This condition often arises from myocardial infarction or ischemia, leading to decreased cardiac output, reduced tissue perfusion, impaired gas exchange, fluid volume imbalance, and decreased functional ability.Heart failure can result from disruptions in the mechanisms that regulate cardiac output...
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Heart Failure II: Pathophysiology01:29

Heart Failure II: Pathophysiology

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Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...
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Related Experiment Video

Updated: Nov 4, 2025

Assessment of Myofilament Ca2+ Sensitivity Underlying Cardiac Excitation-contraction Coupling
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ECSIT is a critical limiting factor for cardiac function.

Linan Xu1, Fiachra Humphries1, Nezira Delagic1

  • 1The Kathleen Lonsdale Institute for Human Health Research, Department of Biology, Maynooth University, Maynooth, Ireland.

JCI Insight
|May 25, 2021
PubMed
Summary
This summary is machine-generated.

Human ECSIT protein is unstable, impacting mitochondrial function and leading to cardiac issues in a humanized mouse model. This study reveals ECSIT

Keywords:
CardiologyCardiovascular diseaseMetabolismMitochondria

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Area of Science:

  • Mitochondrial biology
  • Cellular signaling
  • Cardiovascular pathophysiology

Background:

  • Evolutionarily conserved signaling intermediate in Toll pathways (ECSIT) is crucial for development, immune response, and mitochondrial function.
  • Human ECSIT (hECSIT) is intrinsically labile, unlike its murine counterpart (mEcsit).
  • The functional consequences of hECSIT instability are not well understood.

Purpose of the Study:

  • To investigate the functional impact of hECSIT instability.
  • To create and characterize a humanized mouse model expressing hECSIT.
  • To explore the role of ECSIT in mitochondrial function and cardiac health.

Main Methods:

  • Generation of a transgenic mouse model replacing the murine Ecsit gene with the human ECSIT gene.
  • Assessment of hECSIT protein levels and stability in the humanized mouse.
  • Evaluation of immune cell function (Salmonella clearance, mROS production).
  • Analysis of cardiac phenotype, mitochondrial complex I assembly and activity, oxidative phosphorylation, ATP production, and mitochondrial dynamics in aging mice.
  • Correlation of cardiac fibrosis and damage in humans with ECSIT expression levels.

Main Results:

  • Humanized mice exhibit low hECSIT levels due to intrinsic instability.
  • hECSIT compensates for mEcsit in development and NF-κB activation but impairs Salmonella clearance and mROS production in macrophages.
  • Aging humanized mice develop severe cardiac hypertrophy and premature death.
  • Low hECSIT levels result in reduced mitochondrial complex I assembly/activity, impaired oxidative phosphorylation, and ATP deficiency.
  • Cardiac tissue shows altered mitochondrial dynamics (reduced fusion, increased fission, impaired clearance) and ECSIT plays a cardiomyocyte-intrinsic role in cardioprotection.
  • Low human ECSIT expression correlates with cardiac fibrosis and damage in humans.

Conclusions:

  • ECSIT plays a significant role in cardioprotection.
  • hECSIT instability leads to mitochondrial dysfunction and cardiac pathophysiology.
  • The humanized mouse model is a valuable tool for studying mitochondrial dysfunction and heart disease.
  • ECSIT's role in mitochondrial complex I assembly and function is critical for maintaining cardiac health.