Lysophosphatidic acid (LPA) is an intermediate product of membrane phospholipid metabolism. Recently, LPA has gained attention for its involvement in the pathological processes of certain cardiovascular diseases. The aim of the present study was to clarify the association between the effect of LPA and the immune inflammatory response, and to investigate the effects of LPA on the protein expression levels of connexin 43 during myocardial infarction. Surface electrocardiograms of myocardial infarction rats and isolated rat heart tissue samples were obtained in order to determine the effect of LPA on the incidence of arrhythmia in rats that exhibited changes in immune status. The results demonstrated that the incidence of arrhythmia decreased when the rat immune systems were suppressed, and the incidence of arrhythmia increased when the rat immune systems were enhanced. The concentration levels of tumor necrosis factor (TNF)-alpha were determined by ELISA, and the results demonstrated that LPA induced T lymphocyte synthesis and TNF-alpha release. Using a patch-clamp technique, LPA was shown to increase the current amplitude of the voltage-dependent potassium channels (K-v) and calcium-activated potassium channels (K-Ca) in Jurkat T cells. The protein expression of connexin 43 (Cx43) was determined by immunohistochemical staining. The results indicated that LPA caused the degradation of Cx43 and decreased the expression of Cx43. This effect was associated with the immune status of the rats. There was a further decrease in Cx43 expression in the rats of the immune-enhanced group. To the best of our knowledge, these results provide the first evidence that LPA causes arrhythmia through the regulation of immune inflammatory cells and the decrease of Cx43 protein expression. The present study provided an experimental basis for the treatment of arrhythmia and may guide clinical care.
[1]Jilin Univ, Hosp 1, Dept Thorac Surg, 71 Xinmin St, Changchun 130021, Jilin, Peoples R China.
[2]Jilin Univ, China Japan Union Hosp, Dept Surg, Changchun 130033, Jilin, Peoples R China.
[3]Jilin Univ, China Japan Union Hosp, Dept Anesthesiol, Changchun 130033, Jilin, Peoples R China.
[4]Jilin Univ, Norman Bethune Coll Med, Dept Physiol, 126 Xinmin St, Changchun 130021, Jilin, Peoples R China.
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