Cardiomyocyte Apoptosis is a Non-specific Response of the Heart to Different Types of Alteration

Mikhail Blagonravov ¹ Madina Azova ² Anna Korshunova ¹ Victor Frolov ¹

¹The Department of General Pathology and Pathological Physiology, Medical Faculty, Peoples' Friendship University of Russia, Moscow
²The Department of Biology and General Genetics, Medical Faculty, Peoples' Friendship University of Russia, Moscow

Background: The enhancement of cardiomyocyte apoptosis has been proved for cardiac pathology in the number of previous studies. But it is still poorly understood whether it is a universal response of the myocardium to alteration.

Methods: The experiment was performed on animal models of different myocardial alterations in several groups of rabbits: focal ischemia of the left ventricle (LV) was induced by ligation of the descending branch of the left coronary artery, toxic injury of the myocardium – by diphtheria intoxication, acute overload of the LV – by surgical narrowing of the ascending aorta. Further investigation was carried out on days 1, 3 and 5 after the onset of the pathological processes. The effect of chronic cardiac overload was studied on rabbits with 1, 2 and 4 week renal hypertension provoked by renal ischemia. In all animal groups cardiomyocyte apoptosis was studied in the left and right ventricular myocardium by 2 methods: TUNEL assay and colorimetric evaluation of caspase-3 and caspase-8 activity. Intact rabbits of the same breed and age were used as the controls.

Results: The number of TUNEL-positive cardiomyocyte nuclei significantly increased in both ventricles in all animal groups at different experimental terms. Caspase-3 activity was also considerably higher compared with controls in both ventricles and in all groups. However caspase-8 activity was only significantly increased in the LV myocardium in case of acute cardiac overload.

Conclusion: Cardiomyocyte apoptosis rate increases due to the cardiac damage of different types which might have a negative impact on tissue homeostasis of the myocardium and can be considered as a non-specific response. But in most cases apoptotic signal is transduced by the intrinsic pathway and only in case of acute cardiac overload the enhancement of apoptosis is also triggered by the extrinsic receptor-dependent pathway.