Effects of paroxetine-mediated inhibition of GRK2 expression on depression and cardiovascular function in patients with myocardial infarction.
BACKGROUND
Paroxetine is a selective serotonin reuptake inhibitor utilized in the treatment of depression and anxiety disorders. Recent studies have identified paroxetine as a G protein-coupled receptor kinase-2 (GRK2) inhibitor capable of reversing cardiac dysfunction and remodeling in experimental models of acute myocardial infarction (AMI). We determine the clinical importance of paroxetine on cardiac functions in patients having AMI with depression (AMID) in comparison with fluoxetine, an unrelated selective serotonin reuptake inhibitor that does not inhibit GRK2.


METHODS
Diagnosis of depression was based on the 17-item Hamilton Depression Scale and Self-rating Depression Scale in AMI patients after hospital admission. AMID patients were randomly assigned to paroxetine or fluoxetine for treatment of depression. Heart rate variability and cardiac function were evaluated. GRK2 protein levels were measured using peripheral lymphocytes and Western blot.


RESULTS
GRK2 expression in AMID patients was significantly higher than that in AMI patients without depression. In AMID patients, GRK2 levels were positively correlated with the 17-item Hamilton Depression Scale and the Self-rating Depression Scale scores, and negatively correlated with heart rate variability. Treatment of AMID patients with paroxetine significantly reduced the expression of GRK2, normalized the autonomic nervous system function, and improved cardiac performance. In contrast, fluoxetine normalized the autonomic nervous system but did not reduce the expression of GRK2 nor improved cardiac performance.


CONCLUSIONS
This study suggests that paroxetine is effective for improving cardiac function in patients with AMID and such effect correlates with GRK2 reduction.
Department of Cardiology, Qianfoshan Hospital of Shandong University, Jinan City.
Xiuqing
X
Tian
Department of Cardiology, Qianfoshan Hospital of Shandong University, Jinan City.
Qing
Q
Wang
Department of Physiology, Nanjing University of Chinese Medicine, Nanjing City.
Rui
R
Guo
College of Medicine, Weifang Medical University, Weifang City, People's Republic of China.
Lingling
L
Xu
Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, USA.
Qin M
QM
Chen
Department of Cardiology, Qianfoshan Hospital of Shandong University, Jinan City.
Yinglong
Y
Hou
G protein-coupled receptor kinase-2; acute myocardial infarction; depression; heart rate variability; selective serotonin reuptake inhibitors
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