Clinical & Experimental Cardiology
Open Access
ISSN: 2155-9880
+44 1300 500008
ISSN: 2155-9880
+44 1300 500008
Farahnaz Jazaerijooneghani
Tehran University, Iran
Posters & Accepted Abstracts: J Clin Exp Cardiolog
Background: Lithium has a long history of application as a first line agent in the treatment of bipolar disorder. Cardiovascular effects of lithium have been reported including sick sinus syndrome. Despite multiple molecular targets of lithium have been recognized, the exact mechanism of its action remains unclear. Several studies proposed that lithium exerts some of its biochemical and behavioural effects through disruption of a �²-arrestin-2/AKT/protein phosphatase2A (PP2A) complex signaling. ��-arrestins (�²-arrestin-1 and �²-arrestin-2) can contribute to the progression of fibrotic processes in tissues. Furthermore, �²-arrestin-2 has been shown to inhibit �²-adrenergic receptor (�²-AR) activation in cardiomyocytes as well as cardiac fibroblasts. Aims: Herein, we investigated the subsequent development of cardiac fibrosis and chronotropic responsiveness associated with this compound followed by examining the involvement of �²-arrestin-2 in lithium-mediated effects on the disease process. Methods: Male Wistar rats were treated by lithium chloride 2.5 g/kg, for two to three months orally. After that the atria were isolated and spontaneously beating rate and chronotropic responsiveness to beta-adrenergic stimulation was assessed using standard organ bath. Atrial fibrosis was assessed using staining with hematoxylin and eosin (H&E) for histomorphological characterisation or with Massonâ��s trichrome to visualize collagenous and elastic tissue. The expression collagen type1, alpha1 (COL1A1) and �²-arrestin-2 was assessed in the atria using quantitative RT-PCR. Results: Our data showed that chronotropic responses to isoproterenol were impaired significantly in isolated atria following two months lithium treatment (P<0.001). Furthermore, a significant difference in EC50 of isoproterenol between lithium treated atria (logEC50 = -7.501�±0.05) compared to control atria (logEC50 = -8.966�±0.09) was observed. However, there was no significant difference in the maximum response (Rmax) to isoproterenol in lithium treated group in comparison with control group. Lithium treated rats developed fibrosis in the atria; the observation of three stained sections were as follow: three months lithium treatment: minimal interstitial fibrosis, mild focal interstitial fibrosis, negative for fibrosis; 2 months lithium treatment: mild focal interstitial fibrosis, subendocardial fibrosis, negative for fibrosis; no evidence of fibrosis was seen in control stained sections. The result of data analysis revealed that �²-arrestin-2 mRNA was up-regulated in atria of lithium-treated rats after two or three monthsâ�� treatment as compared with control. The fold change in expression ratio of �²-arrestin-2 in lithium-treated groups versus control was almost 1.5. Furthermore, COL1A1 mRNA expression of rat atria in lithium-treated groups after two or three months treatment were increased 2.53- and 2.04-folds compared with control group, respectively. Conclusion: The present study describes the adverse effect of lithium including chronotropic hypo responsiveness, atrial fibrosis and potential involvement of �²-arrestin-2.
Farahnaz Jazaerijooneghani has completed his/her MD-PhD from Tehran University of Medical Sciences. He/She has been working as Assistant Professor in Tehran University of Medical Sciences, School of Medicine, and Pharmacology Department since 2013. He/She has published more than nine papers in reputed journals and presented posters in EASL Congress (Europe) and Pharma Nutrition Congress (in Philadelphia). He/She has supervised and advised more than 10 medical students, Master and PhD students.
Email: fjazaeri@yahoo.com