Desmin‐free cardiomyocytes and myocardial dysfunction in end stage 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) (rsy0.834; P-0.02) on echocardiogram. A negative relationship (rs y0.688) 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.

Cardiomyocyte mitochondrial oxidative stress and cytoskeletal breakdown in the heart with a primary volume overload

“…For example, some cardiomyocytes were completely devoid of desmin staining, whereas neighboring cardiomyocytes had intact desmin staining along Z lines. A similar desmin staining pattern has been previously described by Di Somma and coworkers (13) in humans with end-stage heart failure due to ischemic cardiomyopathy. Quan-…”

“…In fact, some cardiomyocytes exhibit a near-complete loss of desmin in conjunction with decreased mitochondrial complex IV staining. A patchy, near-total loss of desmin in cardiomyocytes has also been reported in patients with idiopathic dilated cardiomyopathy (13). Disorganization of desmin and mitochondria functional complexes with myofibrils and the sarcoplasmic reticulum have been shown to be present before the onset of cardiac and skeletal muscle failure (3, 6, 24 -28, 36, 38).…”

“…Disorganization of desmin and mitochondria functional complexes with myofibrils and the sarcoplasmic reticulum have been shown to be present before the onset of cardiac and skeletal muscle failure (3, 6, 24 -28, 36, 38). The relation of desmin breakdown to long-term survival and to the severity of LV dysfunction in human heart failure (13,29,32,33) provides further evidence for a nongenetic cause of desmin degradation in the pathophysiology of LV functional deterioration.…”

Possible Cardioprotective Action of Pomegranate Juice Punica Granatum and Propolis Against Myocardial Infarction Induced in Rats.

“…This may be a result of damage of the desmin network in cardiomyocytes. This result is at variance with that reported by (Somma et al, 2004) who reported that a significant decrease in the amount of desmin in diseased myocardial compared to normal tissue.…”

Disruption of desmin-mitochondrial architecture in patients with regurgitant mitral valves and preserved ventricular function

“…We have reported desmin breakdown and increased cardiomyocyte oxidative stress in rats with the primary volume overload of aortocaval fistula and in isolated cardiomyocytes subjected to cyclical stretch (25). Other studies have recently shown a similar disruption and patchy loss of desmin in left ventricles of patients with ischemic cardiomyopathy that is related to the extent of LV dysfunction and poor prognosis (26,27). The relation of desmin breakdown to long-term survival and to severity of LV dysfunction in human heart failure provides compelling evidence for a non-genetic cause of desmin degradation in the pathophysiology of LV functional deterioration in human heart failure and our MR patients.…”