Author(s): Li-Na Han 1 , Shu-Li Guo 1 , Tie-Ling Li [*] 2 , Guo-Lei Ding 1 , Ya-Jing Zhang 1 , Jin-Ling Ma 1
chronic cardiac insufficiency; GATA-3; immune modulation; T-bet; T-lymphocyte subset
Chronic cardiac insufficiency (CCI) is the utmost stage of numerous cardiac diseases spreading extensively and serving as the leading cause of morbidity and mortality in the elderly. Moreover, the number of aging sufferers has increased all over the world. It is traditionally recognized that neurohumoral mechanisms and ventricular remodeling theory represent a crucial factor in the pathophysiology of CCI  . Current research further indicates that inflammatory infiltration and cytokine activation induced by immunological activation is also intensively involved in the occurrence and development of CCI [2,3] . Immunological studies revealed that CD4+ T-lymphocyte activation is the initial step of local or whole-body immunological activation and pronounced Th1-cell activation in the physipathology of CCI  . It has been found that many transcription factors are related to T-helper (Th) differentiation, such as T-bet and GATA-3 , a pair of antagonistic transcription factors during Th0 differentiation  . An immune modulation reagent, thymopentin (TP5), is composed of Arg-Lys-Asp-Val-Tyr and is a valid component of thymopoietin II. It was reported that TP5 can elevate intracellular cAMP levels to invoke and regulate the percentage and proportion of the T-lymphocyte subset, resulting in immunomodulation  . The present study aims to determine the influence of immune therapy on malfunctions of peripheral T-cell differentiation, changes in T-bet /GATA-3 gene expression and imbalance of cytokines in CCI patients, and to explore the molecular mechanism of immune modulation supplementary therapy.
Patients & methods
The CCI patients, who had regular appointments at the Geriatric Cardiovascular Internal Medicine in the Chinese People's Liberation Army (PLA) General Hospital from January 2008 to January 2011, were selected if they met the inclusion criteria. This study was conducted in accordance with the declaration of Helsinki. The study was conducted with approval from the Ethics Committee of the Department of Geriatric Cardiology Internal Medicine, Chinese PLA General Hospital. Written informed consent was obtained from all participants. Diagnosis of chronic heart failure (CHF) was based on clinical history, physical examination and results of echocardiography, chest x-ray, electrocardiography and NT-proBNP. Exclusion criteria included acute and chronic inflammation, other autoimmune disease, unstable angina and acute myocardial infarction within the previous 3 months, rheumatic appearance in rheumatic disease within the previous 3 months, diabetic mellitus, hyperthyrea and other endocrine diseases (immune stimulants were recently used), serious hepatic and renal insufficiency, and malignant tumor. A total of 126 male CCI participants with a mean age of 82 ± 9 (median 81.6; range: 60-95) years and 50 subjects with normal cardiac function with a mean age of 80 ± 10 (median 80.3; range: 57-94) years. Among CCI patients, primary affliction was chronic coronary heart disease in 109, arrhythmia in 65, hypertension in 56, chronic rheumatic in heart disease in three, dilated cardiomyopathy in three and senile degenerative valvular disease in seven subjects. In total, 103 subjects harbored multiple coexisting cardiovascular diseases. Among...