Related Experiment Video
Updated: Apr 10, 2026
11:07
A Murine Model of Myocardial Ischemia-reperfusion Injury through Ligation of the Left Anterior Descending Artery
Published on: April 10, 2014
41.6K
Titin isoform switch in ischemic human heart disease
Ciprian Neagoe1, Michael Kulke, Federica del Monte
1Institute of Physiology and Pathophysiology, University of Heidelberg, Germany.
Circulation
|September 11, 2002
Summary
Chronic ischemia in human hearts causes a titin isoform shift, reducing myofibrillar stiffness and potentially impairing the Frank-Starling mechanism. This shift was also observed in rat hearts after myocardial infarction.
Area of Science:
- Cardiovascular Biology
- Muscle Physiology
- Cardiac Remodeling
Background:
- Ischemia-induced cardiomyopathy increases myocardial stiffness due to collagen and titin.
- Human hearts express N2BA (compliant) and N2B (stiff) titin isoforms, while rat hearts predominantly express N2B.
- The role of titin in ischemia-induced left ventricular stiffening was investigated.
Purpose of the Study:
- To investigate the role of titin isoforms in ischemia-induced left ventricular stiffening.
- To determine the titin isoform ratio in human hearts with coronary artery disease (CAD) and in a rat model of myocardial infarction.
- To assess the impact of titin isoform changes on myofibrillar stiffness.
Main Methods:
- Gel electrophoresis and immunoblotting to analyze titin isoform ratios (N2BA:N2B).
- Immunofluorescence microscopy to examine titin arrangement, collagen, and desmin expression.
- Force measurements on isolated myofibrils to determine passive tension.
Main Results:
- CAD transplant hearts showed a higher N2BA:N2B titin ratio (47:53) compared to non-ischemic transplants (32:68).
- Normal and CAD donor hearts had ~30% N2BA titin; CAD hearts exhibited titin modifications and increased collagen/desmin.
- Ischemic rat hearts developed a distinct N2BA titin band (43%) compared to sham-operated rats (14%).
- Reduced passive tension was observed in myofibrils from CAD hearts with high end-diastolic pressure.
Conclusions:
- A titin isoform switch occurs in chronically ischemic human hearts, favoring the compliant N2BA isoform.
- This shift, also seen in ischemic rat hearts, reduces titin-derived myofibrillar stiffness.
- Titin modifications in ischemic myocardium may impair the heart's ability to utilize the Frank-Starling mechanism.
Related Concept Videos
01:17Ischemic Heart Disease: Overview
4.0K
Ischemic heart disease occurs when the heart's blood supply dwindles, causing an ominous lack of oxygen and nutrients. This deficiency, stemming from reduced or obstructed blood flow, spells danger, leading to heart muscle damage and dysfunction.
Atherosclerosis, the primary malefactor, orchestrates this dangerous condition. It manifests as the accumulation of fatty deposits, akin to insidious plaques, within arterial walls. As time elapses, these plaques metamorphose, hardening and...
Atherosclerosis, the primary malefactor, orchestrates this dangerous condition. It manifests as the accumulation of fatty deposits, akin to insidious plaques, within arterial walls. As time elapses, these plaques metamorphose, hardening and...
4.0K
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
754
Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
754