Cardiac Natriuretic Peptides Gene Expression and Secretion in Inflammation

Abstract

The genetic expression and secretion of the cardiac polypeptide hormones atrial natriuretic factor (ANF or ANP) and brain natriuretic peptide (BNP) have been studied mainly in the context of cardiac diseases associated with neuroendocrine and hemodynamic changes arising from cardiac dysfunction such as in chronic congestive heart failure. In this type of pathology, both ANF and BNP plasma levels change in an approximate coordinated fashion so that the use of these hormones as biomarkers of cardiac disease is, in principle, indistinctive. However, we reported that during an acute cardiac allograft rejection episode, BNP plasma levels can significantly increase in the absence of a similar increase in ANF plasma levels. We tested the hypothesis that these changes were related to cytokines and found that some pro-inflammatory cytokines, including TNFalpha and IL-1beta, selectively promote BNP synthesis and secretion in cultures of neonatal rat ventricular cardiocytes. This effect was found related to increased BNP promoter activity and sensitive to p38 mitogen-activated protein kinase inhibition.In order to determine in vivo if the selective up-regulation of BNP would be observed in inflammatory processes other than acute cardiac allograft rejection, we carried out investigation using the experimental autoimmune myocarditis rat model, which histologically resembles human giant cell myocarditis. It was found that this model is also accompanied by a specific increase in BNP-circulating levels although the cytokines involved seem to differ from those characterized earlier through in vitro studies.Recent studies in humans have found that in sepsis, plasma BNP levels increase in the absence of hemodynamic changes.In conclusion, BNP appears to be regulated uniquely in the setting of an inflammatory process. This sets it apart from ANF in terms of potential roles in the pathogenesis of disease and in its use as a biomarker of cardiac disease.

TNF-αRegulates Natriuretic Peptides and Aquaporins in Human Bronchial Epithelial Cells BEAS-2B

“…The observed selective modulation in ANP and BNP gene expression after TNF- α treatment, in line with other studies in different cell models [19, 49, 50] could be related to a different regulation mechanism at transcriptional level, as suggested by our observation on the different involvement of NF- κ B and MAPKs signaling pathways. In particular, we demonstrated that ANP down-regulation, TNF- α -mediated, occurs via NF- κ B activation pathway, whereas BNP modulation requires ERK 1/2 activation pathway.…”

“…Besides, in vitro studies conducted in rat cardiomyocytes have shown that not only hemodynamic factors, but also neurohumoral factors, activated during heart failure, such as angiotensin II, endothelin and cytokines, cause BNP secretion [42–44]. In addition, in patients with cardiovascular diseases, plasma BNP levels have been shown to be also affected by low-grade inflammation [24] and a selective increase in BNP plasma levels has been proposed as a general feature of inflammation [19]. The lack on any apparent TNF- α dose-depending increase in BNP gene expression that we observed in our system could be due to an autocrine negative feedback action mediated by BNP itself, following binding to the NPR-1 receptor expressed in BEAS-2B cells.…”

“…BNP, secreted from the cardiac ventricles, and atrial natriuretic peptide (ANP), secreted from the cardiac atria, activate the same transmembrane guanylyl cyclase-A/natriuretic peptide receptor-A (NPR-A or NPR-1) [14–17]. In addition to vasodilation, cardiovascular homeostasis, sodium excretion, and inhibition of aldosterone secretion, it is becoming increasingly recognized that NPs possess a much broader range of biological activities, including effects on endothelial function and inflammation [18, 19]. The genetic expression and secretion of ANP and BNP have been studied mainly in the context of cardiac diseases associated with neuroendocrine and hemodynamic changes [12, 13, 20]; however it has been pointed out that changes in BNP also occur in a context of an acute inflammatory process [19, 21–24].…”

Brain Natriuretic Peptide Improves Long-Term Functional Recovery after Acute CNS Injury in Mice

“…This was associated with a concurrent reduction in the number of F4=80-positive microglia and Fluoro-Jade B-positive neurons in bilateral hippocampi following injury, as well improved short-and long-term neurological outcomes. Although these effects are consistent with prior data demonstrating that natriuretic peptides may oppose inflammation (Konig et al, 2007;Ma et al, 2004;Meirovich et al, 2008;Vesely and de Bold, 2009), there are few data on its role in the human brain.…”

Biomarkers and acute brain injuries: interest and limits

“…In addition, a recent study links BNP release to proinflammatory cytokines [29]. Berendes and colleagues [30] and Tomida and colleagues [31] reported an association between plasma BNP concentration and the development of delayed ischaemic neurological deficit (DIND).…”