Cardiac gene expression and systemic cytokine profile are complementary in a murine model of post-ischemic heart failure

After myocardial infarction (MI), activation of the immune system and inflammatory mechanisms, among others, can lead to ventricular remodeling and heart failure (HF). The interaction between these systemic alterations and corresponding changes in the heart has not been extensively examined in the setting of chronic ischemia. The main purpose of this study was to investigate alterations in cardiac gene and systemic cytokine profile in mice with post-ischemic HF. Plasma was tested for IgM and IgG anti-heart reactive repertoire and inflammatory cytokines. Heart samples were assayed for gene expression by analyzing hybridization to AECOM 32k mouse microarrays. Ischemic HF significantly increased the levels of total serum IgM (by 5.2-fold) and total IgG (by 3.6-fold) associated with a relatively high content of anti-heart specificity. A comparable increase was observed in the levels of circulating pro-inflammatory cytokines such as IL-1â (3.8X) and TNF-á (6.0X). IFN-ã was also increased by 3.1-fold in the MI group. However, IL-4 and IL-10 were not significantly different between the MI and sham-operated groups. Chemokines such as MCP-1 and IL-8 were 1.4- and 13-fold increased, respectively, in the plasma of infarcted mice. We identified 2079 well annotated unigenes that were significantly regulated by post-ischemic HF. Complement activation and immune response were among the most up-regulated processes. Interestingly, 21 of the 101 quantified unigenes involved in the inflammatory response were significantly up-regulated and none were down-regulated. These data indicate that post-ischemic heart remodeling is accompanied by immune-mediated mechanisms that act both systemically and locally.

Cardiac gene expression and systemic cytokine profile are complementary in a murine model of post-ischemic heart failure.

After myocardial infarction (MI), activation of the immune system and inflammatory mechanisms, among others, can lead to ventricular remodeling and heart failure (HF). The interaction between these systemic alterations and corresponding changes in the heart has not been extensively examined in the setting of chronic ischemia. The main purpose of this study was to investigate alterations in cardiac gene and systemic cytokine profile in mice with post-ischemic HF. Plasma was tested for IgM and IgG anti-heart reactive repertoire and inflammatory cytokines. Heart samples were assayed for gene expression by analyzing hybridization to AECOM 32k mouse microarrays. Ischemic HF significantly increased the levels of total serum IgM (by 5.2-fold) and total IgG (by 3.6-fold) associated with a relatively high content of anti-heart specificity. A comparable increase was observed in the levels of circulating pro-inflammatory cytokines such as IL-1beta (3.8X) and TNF-alpha (6.0X). IFN-gamma was also increased by 3.1-fold in the MI group. However, IL-4 and IL-10 were not significantly different between the MI and sham-operated groups. Chemokines such as MCP-1 and IL-8 were 1.4- and 13-fold increased, respectively, in the plasma of infarcted mice. We identified 2079 well annotated unigenes that were significantly regulated by post-ischemic HF. Complement activation and immune response were among the most up-regulated processes. Interestingly, 21 of the 101 quantified unigenes involved in the inflammatory response were significantly up-regulated and none were down-regulated. These data indicate that post-ischemic heart remodeling is accompanied by immune-mediated mechanisms that act both systemically and locally.

Anti-inflammatory effect of the hydralcoholic extract of Zingiber officinale rhizomes on rat paw and skin edema.

Plant extracts have been used for centuries as a popular mode of treatment for several health disorders. Over the last ten years, the study of those extracts has attracted attention in different fields of the biological sciences. Ginger, the rhizome of Zingiber officinale Roscoe (Zingiberaceae), is a commom constituent of diet worldwide and it has been reported that its extracts present some pharmacological activities. Here we investigate the effects of the crude hydralcoholic extract of ginger rhizomes on the classical models of rat paw and skin edema. The carrageenan-, compound 48/80- or serotonin-induced rat paw edema were inhibited significantly by the intraperitoneal administration of alcoholic ginger extract. Ginger extract was also effective in inhibiting 48/80-induced rat skin edema at doses of 0.6 and 1.8 mg/site. Rat skin edema induced by substance P or bradikinin was not affected by treatment with Z. officinalle extract. The intraperitoneal administration of ginger extract (186 mg/kg(-1) body wt.) 1 h prior to serotonin injections, reduced significantly the serotonin-induced rat skin edema. Our results demonstrated that crude extract of Zingiber officinale was able to reduce rat paw and skin edema induced by carrageenan, 48/80 compound and serotonin. The antiedematogenic activity seems to be related, at least partially, to an antagonism of the serotonin receptor.

Histamine-potentiating activity in rat anaphylactic pleural fluid: role of serotonin

The identity of the histamine-potentiating activity detected in the rat anaphylactic pleural washing was investigated. Wistar rats of both sexes, weighing 150-200 g, were sensitized by injecting subcutaneously (sc) a mixture of ovalbumin and Al(OH)3 14 days before allergen challenge. In sensitized rats, intrapleural (ipl) injection of ovalbumin (l2 mug/cavity) caused an intense protein exudation. A single ipl administration of compound 48/80 (l2 mug/cavity) exhausted the resident mast cell population and turned the pleural cavity hyporeactive to the allergen challenge performed 5 days later. Allergen-induced exudation occurred in parallel to a dramatic decrease in the amount of cell-stored histamine (from 9.6 ñ 1.4 (N = 8) to 1.3 ñ 0.1 (N = 6) mug/cavity, P<0.001) in the pleural fluid within 10 min. The anaphylactic cell-free pleural washing obtained at this time, as well as histamine at a concentration equivalent to that stored in pleural mast cells (10 mug/cavity), did not induce pleural exudation when injected into normal rats. In contrast the combined administration of histamine and anaphylactic pleural washing led to remarkable pleural exudation, comparable to that obtained with a high dose of histamine (200 mug/cavity) alone. It is noteworthy that the anaphylactic washing from compound 48/80 pretreated rats failed to synergize with histamine. Also, synergism was not reproduced when recipient rats were pretreated with methysergide (50 mug/cavity). Consistently, serotonin (5 mug/cavity) acted synergistically with histamine (1O mug/cavity), producing a greater exudative response than observed with the sum of the effects of each vasoactive amine alone. The results indicate that serotonin accounts for the histamine-potentiating activity noted in the anaphylactic pleural washing, confirming that the synergistic interaction between these vasoactive amines plays a critical role in the rat allergic pleurisy.