Inotropic and lusitropic abnormalities in heart failure

Am, Katz

doi:10.1093/eurheartj/11.suppl_a.27

Cited by 14 publications

(8 citation statements)

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“…, lusitropy. Since β‐adrenergic stimulation also increases HR (tachycardia), the β‐adrenergic‐cAMP‐dependent interplay between inotropy and lusitropy ensures the heart to relax from a stronger contraction in a shorter time, allowing it to adequately fill during the abbreviated diastole (32). Notably, the experiments performed on the isolated papillary muscle also suggest a direct peptide action, independent from any possible alteration in cardiac rhythm and coronary flow rate.…”

Section: Discussionmentioning

confidence: 99%

The novel chromogranin A‐derived serpinin and pyroglutaminated serpinin peptides are positive cardiac β‐adrenergic‐like inotropes

et al. 2012

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Three forms of serpinin peptides, serpinin (Ala26Leu), pyroglutaminated (pGlu)-serpinin (pGlu23Leu), and serpinin-Arg-Arg-Gly (Ala29Gly), are derived from cleavage at pairs of basic residues in the highly conserved C terminus of chromogranin A (CgA). Serpinin induces PN-1 expression in neuroendocrine cells to up-regulate granule biogenesis via a cAMP-protein kinase A-Sp1 pathway, while pGlu-serpinin inhibits cell death. The aim of this study was to test the hypothesis that serpinin peptides are produced in the heart and act as novel β-adrenergic-like cardiac modulators. We detected serpinin peptides in the rat heart by HPLC and ELISA methods. The peptides included predominantly Ala29Gly and pGlu-serpinin and a small amount of serpinin. Using the Langendorff perfused rat heart to evaluate the hemodynamic changes, we found that serpinin and pGlu-serpinin exert dose-dependent positive inotropic and lusitropic effects at 11-165 nM, within the first 5 min after administration. The pGlu-serpinin-induced contractility is more potent than that of serpinin, starting from 1 nM. Using the isolated rat papillary muscle preparation to measure contractility in terms of tension development and muscle length, we further corroborated the pGlu-serpinin-induced positive inotropism. Ala29Gly was unable to affect myocardial performance. Both pGlu-serpinin and serpinin act through a β1-adrenergic receptor/adenylate cyclase/cAMP/PKA pathway, indicating that, contrary to the β-blocking profile of the other CgA-derived cardiosuppressive peptides, vasostatin-1 and catestatin, these two C-terminal peptides act as β-adrenergic-like agonists. In cardiac tissue extracts, pGlu-serpinin increased intracellular cAMP levels and phosphorylation of phospholamban (PLN)Ser16, ERK1/2, and GSK-3β. Serpinin and pGlu-serpinin peptides emerge as novel β-adrenergic inotropic and lusitropic modulators, suggesting that CgA and the other derived cardioactive peptides can play a key role in how the myocardium orchestrates its complex response to sympathochromaffin stimulation.

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Section: Discussionmentioning

confidence: 99%

The novel chromogranin A‐derived serpinin and pyroglutaminated serpinin peptides are positive cardiac β‐adrenergic‐like inotropes

et al. 2012

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“…According to a mechanism common for cAMP elevating agonists (Koshimizu et al, 2010), serpinin and pGlu-serpinin might bind to a G protein-coupled receptor (GPCR) enhancing the cardiac cAMP levels, with consequent hemodynamic effects that are indeed abolished by selective inhibition of AD and PKA. The major downstream targets of the AD-cAMP signaling are PKAs which phosphorylate a number of proteins, including SERCA and its associated modulatory protein, PLN, both crucial regulators of myocardial inotropy and lusitropy (Katz, 1990). SERCA-dependent Ca ++ uptake within SR promotes cation removal during diastole, thus affecting relaxation and the subsequent contraction (Satoh et al, 2011).…”

Section: Cardiac Actions Of Serpininmentioning

confidence: 99%

The surging role of Chromogranin A in cardiovascular homeostasis

2014

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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.

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“…In fact, altered lusitropy is one of the hallmarks of the failing myocardium. 22 It is evident that the increased relaxation rate of the myocardium plays a central role in the ␤-adrenergic stimulation-mediated enhanced cardiac pump performance in both normal and diseased heart. With the advent of genetic technologies directed at the heart, significant inroads have been made toward the molecular mechanisms of accelerated relaxation kinetics of the myocardium during ␤-adrenergic stimulation.…”

Section: Functional Significance Of Covalent Modification Of Troponinmentioning

confidence: 99%

Covalent and Noncovalent Modification of Thin Filament Action

Metzger

Westfall

2004

Circulation Research

158

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Key Words: calcium Ⅲ phosphorylation Ⅲ myocardium Ⅲ contractility S ince its discovery some 40 years ago, troponin has been a focal point for studies on the mechanisms of calcium regulation of striated muscle function. 1,2 Over 6000 articles have been published on troponin and thin filament regulation, and appropriately, there have been numerous outstanding reviews on troponin and striated muscle regulatory function. [2][3][4][5][6][7] The scope of the present review is on posttranslational modifications of the thin filament, with a primary focus on troponin. Specifically, the first and major part of this review discusses how covalent modification of troponin, largely through phosphorylation by protein kinases A and C, affects troponin and muscle performance in vitro and in vivo. In the second part, we overview how noncovalent modification of troponin, focusing on muscle acidification, alters troponin's function at the cellular, organ, and whole animal levels. This review is intended to complement the companion articles in this series that address additional vital aspects of troponin and thin filament regulatory function in health and disease. Thin Filament Regulatory SystemThe thin filament regulatory system of cardiac and skeletal muscle consists of a highly ordered assembly of proteins (Figure 1). [3][4][5]7 This regulatory machinery is directly responsible for governing the force-generating interactions between myosin and actin. The thin filament structure of mammalian skeletal and cardiac muscle is dominated by actin, a globular protein that, under physiological conditions, polymerizes into elongated filaments of double helical strands. Residing in the groove formed between actin strands is tropomyosin (Tm), an elongated protein that spans seven actin monomers and is polymerized head-to-tail along the actin filament. Associated with each Tm is troponin, a globular protein complex con-

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Inotropic and lusitropic abnormalities in heart failure

Cited by 14 publications

References 0 publications

The novel chromogranin A‐derived serpinin and pyroglutaminated serpinin peptides are positive cardiac β‐adrenergic‐like inotropes

The novel chromogranin A‐derived serpinin and pyroglutaminated serpinin peptides are positive cardiac β‐adrenergic‐like inotropes

The surging role of Chromogranin A in cardiovascular homeostasis

Covalent and Noncovalent Modification of Thin Filament Action

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