Involvement of the serotonin 5-HT2B receptor in cardiac hypertrophy linked to sympathetic stimulation control of interleukin-6, interleukin-1 beta, and tumor necrosis factor-alpha cytokine production by ventricular fibroblasts

Article

关键词: BETA-ADRENERGIC STIMULATION;    PRESSURE-OVERLOAD;    MYOCARDIAL-INFARCTION;    GENE-EXPRESSION;    HEART-FAILURE;    KNOCKOUT MICE;    2B RECEPTOR;    RAT HEARTS;    IN-VIVO;    BLOCKADE;   

DOI  :  10.1161/01.CIR.0000139856.20505.57

来源: SCIE

【 摘 要 】

Background - The serotonergic 5-HT2B receptor regulates cardiomyocyte development and growth. A putative contribution of this receptor to fibroblast-dependent cardiac function has not been identified. Methods and Results - By mimicking sympathetic stimulation with chronic isoproterenol perfusion in vivo, we found that mice developed a cardiac hypertrophy, which was prevented by exposure to the 5-HT2B receptor antagonists SB206553 or SB215505 or in 5-HT2B receptor-knockout mice. The isoproterenol-induced hypertrophy was associated with an increase in the plasma levels of interleukin-1beta and tumor necrosis factor-alpha but not interleukin-6. In contrast, the plasma isoproterenol-induced cytokine increase was not observed in either 5-HT2B receptor - mutant or wild-type mice perfused with isoproterenol + SB206553. We demonstrated that stimulation of wild-type cardiac fibroblasts by isoproterenol markedly increased the production of the interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha cytokines. Strikingly, we found that this isoproterenol-induced cytokine production was abolished by SB206553 or in 5-HT2B receptor - knockout fibroblasts. Serotonin also stimulated production of the 3 cytokines in wild-type fibroblasts, which was effectively reduced in 5-HT2B receptor-knockout fibroblasts. Conclusions - Our results demonstrate for the first time that 5-HT2B receptors are essential for isoproterenol-induced cardiac hypertrophy, which involves the regulation of interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha cytokine production by cardiac fibroblasts.

【 授权许可】

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