Abstract
BackgroundPharmacological and gene ablation studies have demonstrated the crucial role of the endocrine function of the heart as mediated by the polypeptide hormones ANF and BNP in the maintenance of cardiovascular homeostasis. The importance of these studies lies on the fact that hypertension and chronic congestive heart failure are clinical entities that may be regarded as states of relative deficiency of ANF and BNP. These hormones are produced by the atrial muscle cells (cardiocytes), which display a dual secretory/muscle phenotype. In contrast, ventricular cardiocytes display mainly a muscle phenotype. Comparatively little information is available regarding the genetic background for this important phenotypic difference with particular reference to the endocrine function of the heart. We postulated that comparison of gene expression profiles between atrial and ventricular muscles would help identify gene transcripts that underlie the phenotypic differences associated with the endocrine function of the heart.ResultsComparison of gene expression profiles in the rat heart revealed a total of 1415 differentially expressed genes between the atria and ventricles based on a 1.8 fold cut-off. The identification of numerous chamber specific transcripts, such as ANF for the atria and Irx4 for the ventricles among several others, support the soundness of the GeneChip data and demonstrates that the differences in gene expression profiles observed between the atrial and ventricular tissues were not spurious in nature. Pathway analysis revealed unique expression profiles in the atria for G protein signaling that included Gαo1, Gγ2 and Gγ3, AGS1, RGS2, and RGS6 and the related K+ channels GIRK1 and GIRK4. Transcripts involved in vesicle trafficking, hormone secretion as well as mechanosensors (e.g. the potassium channel TREK-1) were identified in relationship to the synthesis, storage and secretion of hormones.ConclusionThe data developed in this investigation describes for the first time data on gene expression particularly centred on the secretory function of the heart. This provides for a rational approach in the investigation of determinants of the endocrine of the heart in health and disease.
Highlights
Pharmacological and gene ablation studies have demonstrated the crucial role of the endocrine function of the heart as mediated by the polypeptide hormones ANF and BNP in the maintenance of cardiovascular homeostasis
This information is important to understand why under chronic conditions of hemodynamic overload such as in chronic congestive heart failure, the secretion of ANF and BNP is insufficient as demonstrated by the fact that patients that receive exogenous hormone benefit from the unloading of the heart induced by therapeutic administration of either of the hormones [1]
The bulk of atrial cardiocytes have, in addition to features commonly associated with striated cardiac muscle cell cytology, organelles that are normally found in cells engaged in the synthesis, vectorial transport and secretion of polypeptide hormones
Summary
Pharmacological and gene ablation studies have demonstrated the crucial role of the endocrine function of the heart as mediated by the polypeptide hormones ANF and BNP in the maintenance of cardiovascular homeostasis The importance of these studies lies on the fact that hypertension and chronic congestive heart failure are clinical entities that may be regarded as states of relative deficiency of ANF and BNP. The majority of these investigations have concentrated on pharmacological interventions but much remains to be determined regarding specific genes involved in cardiocyte secretory function This information is important to understand why under chronic conditions of hemodynamic overload such as in chronic congestive heart failure, the secretion of ANF and BNP is insufficient as demonstrated by the fact that patients that receive exogenous hormone benefit from the unloading of the heart induced by therapeutic administration of either of the hormones [1]. Through the present work we have defined genes that may be fitted within a more detailed view of cardiac endocrine function
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