Arginine Vasopressin-mediated Cardiac Differentiation

Abstract

Despite the existence of a functional arginine vasopressin (AVP) system in the adult heart and evidence that AVP induces myogenesis, its significance in cardiomyogenesis is currently unknown. In the present study, we hypothesized a role for AVP in cardiac differentiation of D3 and lineage-specific embryonic stem ( The neurohypophyseal hormone arginine vasopressin (AVP) 2 is essential for cardiovascular homeostasis. AVP is involved in the regulation of body fluid osmolality, blood volume and pressure via the stimulation of specific receptors with distinct pharmacological profiles and intracellular second messengers (1, 2). AVP activity is mediated by at least 3 different G-protein-coupled receptors, called V1a, V1b (also known as V3), and V2. The V1a receptor (V1aR), abundantly expressed in vascular smooth muscle cells, hepatocytes, and platelets, and V1b receptor (V1bR), predominantly found in the anterior pituitary, are linked to the phosphoinositol signaling pathway with intracellular calcium as second messenger. In contrast, the V2 receptor (V2R) is coupled to the adenylate cyclase signaling with intracellular cAMP as the second messenger. V2R has long been recognized to be exclusively expressed in kidney (3), but there is increasing evidence of extrarenal V2R expression (4 -6). Recently, a role was suggested for AVP as a novel myogenesis-promoting factor (7,8). AVP was shown to regulate the expression of early and late myogenic differentiation markers in cultured myogenic cell lines. In addition, studies on endothelial and osteoblast-like cells indicated a potential involvement of nitric oxide (NO) in proliferation pathways mediated by AVP (6, 9). NO is a universal signaling molecule implicated in many physiological and pathophysiological functions. In the adult heart, NO is involved in the regulation of heart rate, contractility, and coronary perfusion. Moreover, increasing evidence indicates an important role of NO in cardiac differentiation (10).In a previous report, we addressed mechanisms promoting differentiation of the mammalian cardiac conduction system in murine embryonic stem (ES) cells (11). Cardiomyogenic differentiation in ES cells is manifested by the appearance of spontaneously and rhythmically beating cardiomyocytes within developing embryoid bodies (EBs). Differentiation of ES cells to the cardiac lineage provides a model for the exploration of mechanisms and genes involved in the earliest steps of cardiac development.Therefore, the aim of this study was to undertake a detailed analysis of the cardiomyogenic actions of AVP during ES cell differentiation and the role of NO in AVP-mediated pathways. To determine whether AVP specifically affects the differentiation of atrial or ventricular phenotypes, we used ES cell clones expressing the green fluorescent protein (GFP) gene under the control of cardiac-restricted atrial natriuretic peptide (Anp) or * This work was supported by grants from Deutsche Forschungsgemeinschaft (to N. G. and U. C. H.) and the Canadian Institutes of Health Research and...

Arginine vasopressin receptor signaling and functional outcomes in heart failure

“…V1AR-mediated protein synthesis occurs in a PLC- and PKC-dependent manner involving elevated Ca 2+ responses and c-fos expression [35, 89, 125], and it has been shown that AVP strongly regulates the GATA-4 transcription factor in hypertrophied cardiomyocytes [127]. Interestingly, V1AR regulation of GATA-4 may also aid in ventricular precursor differentiation and maturation as V1AR mediates GATA-4 during D3 embryonic stem cell differentiation via the NOS pathway [128]. Studies examining the expression of vasopressin receptors on rat hearts have shown that although V2R expression is barely detectable in adult rat hearts, its expression increases until post-natal day 5 and then declines [129].…”

“…Studies examining the expression of vasopressin receptors on rat hearts have shown that although V2R expression is barely detectable in adult rat hearts, its expression increases until post-natal day 5 and then declines [129]. The V2R expression and presence of AVP in maturing hearts suggests that V2R may play a role in cardiac development and maturation; indeed, while V1AR is mainly responsible for ventricular differentiation of embryonic stem cells, V2R were shown to modulate atrial precursor cell differentiation [128]. …”

Arginine vasopressin inhibits adipogenesis in human adipose-derived stem cells

“…We demonstrated that undifferentiated hASCs and differentiated adipocytes express the V1a receptor, but not the V1b or V2. This observation differs from mouse embryonic stem cells that express all three receptor subtypes (Gassanov et al, 2007). It is possible that the pluripotent nature of embryonic stem cells compared to multipotent adult stem cells may be accountable for this variation.…”

“…To investigate the effect of AVP on adipogenesis, we supplemented the differentiation medium with 100 nM AVP which enhances differentiation of other cell types (Gassanov et al, 2007; Gutkowska et al, 2007; Nervi et al, 1995). AVP supplementation reduced lipid droplet accumulation as determined by ORO staining (Fig.…”

“…Other studies revealed that the hormone is capable of stimulating cellular growth and proliferation. Despite the identification of AVP receptors in stem cells (Gassanov et al, 2007), its function in Ca 2+ signaling and differentiation remains largely unexplored. We investigated the mechanism of AVP signaling and its impact on adipocyte differentiation in hASCs, which is a well-accepted stem cell type for adipogenic studies (Bourin et al, 2013).…”