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Published on: April 21, 2014
Desmin-free cardiomyocytes and myocardial dysfunction in end stage heart failure
S Di Somma1, M P Di Benedetto, G Salvatore
1Medical Department, II Medical School University La Sapienza, Sant' Andrea Hospital, Rome, Italy. sdisomma@unina.it
Insights
Patients with end-stage heart failure from ischemic cardiomyopathy have reduced desmin in heart muscle cells. This desmin deficiency is linked to poorer cardiac function, impacting ejection fraction and pressure.
Area of Science:
- Cardiology
- Cell Biology
- Biochemistry
Background:
- Desmin is a crucial cytoskeletal protein in cardiomyocytes.
- Alterations in desmin may contribute to heart failure pathogenesis.
- Ischemic cardiomyopathy (ICM) leads to end-stage heart failure.
Purpose of the Study:
- To quantify desmin levels in myocardial tissue of ICM patients.
- To investigate the association between desmin content and cardiac function in ICM.
- To compare desmin expression in ICM hearts versus controls.
Main Methods:
- Analysis of 18 explanted hearts from ICM patients and control tissues.
- Light and confocal immunochemistry for desmin localization and quantification.
- Real-time PCR to measure desmin mRNA levels.
- Echocardiography and right heart catheterization for cardiac function assessment.
Main Results:
- Significantly lower desmin-positive myocytes observed in ICM hearts compared to controls (P<0.01).
- Reduced desmin content confirmed by real-time PCR in ICM patients (P<0.01).
- Negative correlation between desmin-negative cardiomyocytes and ejection fraction (r=-0.834, P<0.02).
- Negative relationship between desmin-negative myocytes and capillary wedge pressure (r=-0.688).
Conclusions:
- End-stage heart failure in ICM is associated with a decreased number of desmin-positive myocytes.
- Deficiency in cytoskeletal desmin correlates with impaired cardiac function.
- Desmin may play a significant role in the pathophysiology of ischemic heart failure.
Abstract:
Our aim was to evaluate the desmin content in the myocardial tissue of patients with end-stage heart failure of ischaemic origin and to assess its role on cardiac function. We studied 18 explanted hearts from patients transplanted for end-stage heart failure due to ischaemic cardiomyopathy (ICM). Control myocardial tissue was obtained from the cardiac biopsies of six women with breast cancer taken prior to commencing chemotherapy with anthracyclines, four male donors for heart transplantation and two autoptic hearts from patients who died due to non-cardiac events. Myocardial tissue, obtained from the left ventricle (remote zone from infarcted area), was analyzed by light and confocal immunochemistry (desmin) microscopy. The desmin content of myocardial tissue was obtained by real-time PCR. Cardiac function was evaluated by echocardiographic and right heart catheterization data, obtained before heart transplantation. Confocal microscopy evaluation showed a significant decrease in the number of desmin-positive myocytes (P<0.01) in ICM hearts compared to controls. At real-time PCR evaluation, there was a reduction (P<0.01) in desmin content in the ICM patients compared to controls. A negative correlation was found between desmin-free cardiomyocytes and ejection fraction (EF) (r=-0.834; P<0.02) on echocardiogram. A negative relationship (r=-0.688) was also found between desmin-negative myocytes and capillary wedge pressure. In conclusion, the myocardial tissue of patients with end-stage heart failure of ischaemic origin, shows a decreased number in desmin-positive myocytes at immunochemistry evaluation compared to normal individuals. This deficiency in cytoskeletal intermediate filament content is associated with reduced cardiac function.
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