The effects of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 during myocardial ischemia/reperfusion in a model of rats with depression

BMC Psychiatry, Dec 2014

Background Major depressive disorder (MDD) is an independent risk factor for coronary heart disease (CHD), and influences the occurrence and prognosis of cardiovascular events. Although there is evidence that antidepressants may be cardioprotective after acute myocardial infarction (AMI) comorbid with MDD, the operative pathophysiological mechanisms remain unclear. Our aim was therefore to explore the molecular mechanisms of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 in a rat model of depression during myocardial ischemia/reperfusion (I/R). Methods Rats were divided randomly into 3 groups (n = 8): D group (depression), DI/R group (depression with myocardial I/R) and escitalopram + DI/R group. The rats in all three groups underwent the same chronic mild stress and separation for 21 days, at the same time, in the escitalopram + DI/R group, rats were administered escitalopram by gavage (10 mg/kg/day). Ligation of the rat’s left anterior descending branch was done in the myocardial I/R model. Following which behavioral tests were done. The size of the myocardial infarction was detected using 1.5% TTC dye. The Tunel method was used to detect apoptotic myocardial cells, and both the Rt-PCR method and immunohistochemical techniques were used to detect the expression of Bcl–2 and Bax. Results Compared with the D and DI/R groups, rats in Escitalopram + DI/R group showed significantly increased movements and sucrose consumption (P < .01). Compared with the DI/R group, the myocardial infarct size in the escitalopram + DI/R group was significantly decreased (P < .01). Compared with the D group, there were significantly increased apoptotic myocardial cells in the DI/R and escitalopram + DI/R groups (P < .01); however compared with the DI/R group, apoptotic myocardial cell numbers in the escitalopram + DI/R group were significantly decreased (P < .01). Compared with the DI/R group, there was a down-regulated Bax:Bcl-2 ratio in the escitalopram + DI/R group (P < .01). Conclusions These results suggest that in patients with AMI comorbid with MDD, there is an increase in pro-apoptotic pathways that is reversed by escitalopram. This suggests that clinically escitalopram may have a direct cardioprotective after acute myocardial infarction.

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The effects of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 during myocardial ischemia/reperfusion in a model of rats with depression

Yiming Wang 1 Hongming Zhang Fangxian Chai 1 Xingde Liu 0 Michael Berk 0 Department of Cardiology, Hospital Affiliated to Medical University , 28 Guiyi Street, Guiyang City, Guizhou 550004 , China 1 Department of Psychiatry, Hospital Affiliated to Guiyang Medical University , Guiyang, Guizhou 550004 , China Background: Major depressive disorder (MDD) is an independent risk factor for coronary heart disease (CHD), and influences the occurrence and prognosis of cardiovascular events. Although there is evidence that antidepressants may be cardioprotective after acute myocardial infarction (AMI) comorbid with MDD, the operative pathophysiological mechanisms remain unclear. Our aim was therefore to explore the molecular mechanisms of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 in a rat model of depression during myocardial ischemia/reperfusion (I/R). Methods: Rats were divided randomly into 3 groups (n = 8): D group (depression), DI/R group (depression with myocardial I/R) and escitalopram + DI/R group. The rats in all three groups underwent the same chronic mild stress and separation for 21 days, at the same time, in the escitalopram + DI/R group, rats were administered escitalopram by gavage (10 mg/kg/day). Ligation of the rat's left anterior descending branch was done in the myocardial I/R model. Following which behavioral tests were done. The size of the myocardial infarction was detected using 1.5% TTC dye. The Tunel method was used to detect apoptotic myocardial cells, and both the Rt-PCR method and immunohistochemical techniques were used to detect the expression of Bcl-2 and Bax. Results: Compared with the D and DI/R groups, rats in Escitalopram + DI/R group showed significantly increased movements and sucrose consumption (P < .01). Compared with the DI/R group, the myocardial infarct size in the escitalopram + DI/R group was significantly decreased (P < .01). Compared with the D group, there were significantly increased apoptotic myocardial cells in the DI/R and escitalopram + DI/R groups (P < .01); however compared with the DI/R group, apoptotic myocardial cell numbers in the escitalopram + DI/R group were significantly decreased (P < .01). Compared with the DI/R group, there was a down-regulated Bax:Bcl-2 ratio in the escitalopram + DI/R group (P < .01). Conclusions: These results suggest that in patients with AMI comorbid with MDD, there is an increase in pro-apoptotic pathways that is reversed by escitalopram. This suggests that clinically escitalopram may have a direct cardioprotective after acute myocardial infarction. - Background Cardiovascular disease is a major driver of mortality globally, and depression a major driver of morbidity. Coronary heart disease (CHD) is the most common type of cardiovascular disease, and acute myocardial ischemia (AMI) is the classically emergent expression of CHD with an attendant mortality risk. With the development of an increasing understanding of the biology-psychology-social medicine nexus, there is deeper understanding of the risk factors of CHD. There is a relationship between social and psychological factors with CHD and cardiac events, such that high incident rates of depression and anxiety have been found in CHD patients [1], and depression has been proved to be an independent risk factor for CHD, influencing the occurrence and prognosis of cardiovascular events [2]. The mortality rate in patients with CHD and depression is higher than that in patients with CHD only [3]. Our original study [4] suggested that active proapoptotic pathways might be involved in the nexus between myocardial infarction and depression. It is unclear whether antidepressant therapy should be included in the management of AMI patients complicated by depression. It is of clinical and theoretical importance to have effective preventive and treatment strategies for depressive patients complicated by AMI. This has the potential to both improve the survival rates of AMI patients and reduce the consumption of limited medical resources. Currently emergency percutaneous coronary intervention (PCI) has become a routine clinical treatment for AMI, but patients receiving PCI treatment risk postoperative damage such as myocardial ischemia and reperfusion [5]. Although there are some data on the use of antidepressants in myocardial infarction (MI) comorbid with major depressive disorder [6], the pathophysiological processes are unclear. Escitalopram is a widely used antidepressant, but its effectiveness in AMI patients complicated with depression awaits further studies. Our aim was to explore the molecular mechanisms of escitalopram on myocardial apoptosis during myocardial ischemia/reperfusion in a rat model of depression, specifically the expression of Bax and Bcl-2. It was hoped this might illuminate mechanisms and treatment for AMI patients complicated by depression. Methods Subjects Male Sprague-Dawley rats (n = 24, weighing 250 g 20 g) were used for th (...truncated)


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Yiming Wang, Hongming Zhang, Fangxian Chai, Xingde Liu, Michael Berk. The effects of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 during myocardial ischemia/reperfusion in a model of rats with depression, BMC Psychiatry, 2014, pp. 349, 14, DOI: 10.1186/s12888-014-0349-x