ABSTRACT
The involvement of Chromogranin A (CgA) in the cardiovascular function regulation is attributed to its function as a prohormone. Several studies indicated that CgA-derived peptides, particularly Vasostatin-1 (VS-1) and Catestatin (CST), exert signaling effects in numerous organs/systems, including the cardiovascular system. This review focuses on the recently described signaling pathways activated by VS-1 and CST, giving insights into the mechanisms at the basis of their cardiac negative inotropic action, their vasodilator effects and their cardioprotective role observed in different experimental conditions. Accumulated evidences provided convincing support for VS-1 and CST as vasoactive peptides indirectly acting on cardiomyocytes through a Ca(2+)-independent/PI3-K-dependent NO release from endothelial cells. This pathway is supposed to be triggered by the interaction of these peptides with the plasma membrane. The premise of these studies grounds on the biochemical features of VS-1 and CST, which are structurally characterized by amphipathic properties and the ability to interact with mammalian and microbial membranes. On the other hand, recent data obtained in both isolated heart and isolated cardiomyocytes suggest that the VS-1 and CST-mediated cardioprotective effects are primarily direct on the myocardium, rather than endothelium-dependent. Anyway, both direct and indirect pathways seem to be characterized by the absence of specific membrane receptors on target cells, highlighting intriguing novelties in the topic of cell signaling, in particular respect to an hypothetical receptor-independent eNOS activation.
Subject(s)
Chromogranin A/metabolism , Endothelium, Vascular/metabolism , Peptide Fragments/metabolism , Endocytosis , Humans , Myocytes, Cardiac/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type III/metabolism , Signal TransductionABSTRACT
Chromogranin A (CGA), produced by human and rat myocardium, generates several biologically active peptides processed at specific proteolytic cleavage sites. A highly conserved cleavage N-terminal site is the bond 64-65 that reproduces the native rat CGA sequence (rCGA1-64), corresponding to human N-terminal CGA-derived vasostatin-1. rCGA1-64 cardiotropic activity has been explored in rat cardiac preparations. In Langendorff perfused rat heart, rCGA1-64 (from 33 nM) induced negative inotropism and lusitropism as well as coronary dilation, counteracting isoproterenol (Iso) - and endothelin-1 (ET-1) -induced positive inotropic effects and ET-1-dependent coronary constriction. rCGA1-64 also depressed basal and Iso-induced contractility on rat papillary muscles, without affecting calcium transients on isolated ventricular cells. Structure-function analysis using three modified peptides on both rat heart and papillary muscles revealed the disulfide bridge requirement for the cardiotropic action. A decline in Iso intrinsic activity in the presence of the peptides indicates a noncompetitive antagonistic action. Experiments on rat isolated cardiomyocytes and bovine aortic endothelial cells indicate that the negative inotropism observed in rat papillary muscle is probably due to an endothelial phosphatidylinositol 3-kinase-dependent nitric oxide release, rather than to a direct action on cardiomyocytes. Taken together, our data strongly suggest that in the rat heart the homologous rCGA1-64 fragment exerts an autocrine/paracrine modulation of myocardial and coronary performance acting as stabilizer against intense excitatory stimuli.
Subject(s)
Chromogranin A/metabolism , Coronary Vessels/metabolism , Endothelial Cells/metabolism , Myocardial Contraction/physiology , Myocytes, Cardiac/metabolism , Nitric Oxide/metabolism , Papillary Muscles/metabolism , Vasodilation/physiology , Animals , Aorta/cytology , Aorta/metabolism , Autocrine Communication/drug effects , Autocrine Communication/physiology , Calcium/metabolism , Cardiotonic Agents/pharmacology , Cattle , Chromogranin A/pharmacology , Endothelial Cells/cytology , Endothelin-1/pharmacology , Humans , Isoproterenol/pharmacology , Male , Myocardial Contraction/drug effects , Myocytes, Cardiac/cytology , Papillary Muscles/cytology , Paracrine Communication/drug effects , Paracrine Communication/physiology , Phosphatidylinositol 3-Kinases/metabolism , Rats , Rats, Wistar , Structure-Activity Relationship , Vasodilation/drug effectsABSTRACT
A study of 60 femoral prosthetic components removed after 1-20 years allowed us to study the behaviour of the metallic surface in real life conditions. Changes were observed exclusively in cemented prostheses. They consisted of corrosion phenomena characteristic of the components of steel EN 58 J and 316 S, and wear phenomena secondary to mobilisation. The latter were observed in steel components as well as in those in Co-Cr alloy. The areas of corrosion in the steel prostheses were characteristically distributed, indicating a combination of causal factors, including an insufficient capacity of passivation of the metal and the particular situation of the cement-to-metal interface.
Subject(s)
Hip Prosthesis/standards , Chromium Alloys/standards , Corrosion , Equipment Failure , Humans , Steel/standards , Stress, Mechanical , Titanium/standardsABSTRACT
An investigation was conducted to compare the effect of practice on the motor performance of older adults with that of college-aged adults. The temporal location of knowledge of results was varied during the practice in an attempt to ascertain the relationship between information storage/processing capacity and practice effect. Analysis of variance revealed motor performance proficiency differences favoring the younger adults but no difference between age groups in the pattern of performance change associated with practice. The proficiency differences could partially be explained in terms of older adults' information processing limitations.
Subject(s)
Aging , Psychomotor Performance , Adult , Aged , Analysis of Variance , Female , Humans , Learning , Male , Mental ProcessesABSTRACT
The purpose of this study was to determine how individuals learned a motor skill having temporal and spatial parameters. For scores of 10 adult males one-way repeated-measures multivariate analysis indicated that subjects learned the skill but follow-up analysis showed acquisition occurred on accuracy only. Some processing limitations were possible with the number of trials a possible limiting factor.
