Abstract
Together with Chromogranin B and Secretogranins, Chromogranin A (CGA) is stored in secretory (chromaffin) granules of the diffuse neuroendocrine system and released with noradrenalin and adrenalin. Co-stored within the granule together with neuropeptideY, cardiac natriuretic peptide hormones, several prohormones and their proteolytic enzymes, CGA is a multifunctional protein and a major marker of the sympatho-adrenal neuroendocrine activity. Due to its partial processing to several biologically active peptides, CGA appears an important pro-hormone implicated in relevant modulatory actions on endocrine, cardiovascular, metabolic, and immune systems through both direct and indirect sympatho-adrenergic interactions. As a part of this scenario, we here illustrate the emerging role exerted by the full-length CGA and its three derived fragments, i.e., Vasostatin 1, catestatin and serpinin, in the control of circulatory homeostasis with particular emphasis on their cardio-vascular actions under both physiological and physio-pathological conditions. The Vasostatin 1- and catestatin-induced cardiodepressive influences are achieved through anti-beta-adrenergic-NO-cGMP signaling, while serpinin acts like beta1-adrenergic agonist through AD-cAMP-independent NO signaling. On the whole, these actions contribute to widen our knowledge regarding the sympatho-chromaffin control of the cardiovascular system and its highly integrated “whip-brake” networks.
Highlights
The granins are a structurally and functionally related family of proteins including Chromogranin A (CGA), Chromogranin B (CGB) and Secretogranins (SG) II-VII which are stored in secretory granules of the diffuse neuroendocrine system and released together with noradrenalin and adrenalin (Winkler and Fischer-Colbrie, 1992; Montero-Hadjadje et al, 2008; Bartolomucci et al, 2011)
Studies in the past 15 years have convincingly revealed the cardiovascular activities of CGA and its derived peptides vasostatin 1 (VS-1), CST and serpinin, along with their striking adreno-sympathetic regulatory influences
This knowledge, which has widened the prohormone/cytokine profile of CGA, has been paralleled and integrated by a growing number of clinical studies that have documented the biomedical implications of CGA and its peptides in various cardiovascular diseases, in relation to their diagnostic and prognostic value
Summary
Co-stored within the granule together with neuropeptideY, cardiac natriuretic peptide hormones, several prohormones and their proteolytic enzymes, CGA is a multifunctional protein and a major marker of the sympatho-adrenal neuroendocrine activity. Due to its partial processing to several biologically active peptides, CGA appears an important pro-hormone implicated in relevant modulatory actions on endocrine, cardiovascular, metabolic, and immune systems through both direct and indirect sympatho-adrenergic interactions. The Vasostatin 1- and catestatin-induced cardiodepressive influences are achieved through anti-beta-adrenergic-NO-cGMP signaling, while serpinin acts like beta1-adrenergic agonist through AD-cAMP-independent NO signaling. On the whole, these actions contribute to widen our knowledge regarding the sympatho-chromaffin control of the cardiovascular system and its highly integrated “whip-brake” networks
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