Chromogranin A and Its Fragments in the Critically Ill: An Expanding Domain of Interest for Better Care
Life-threatening diseases challenge immunity with a release of chromogranins. This report focuses on Chromogranin A (CGA) and some of its derived peptides in critically ill patients, with attention paid to their potential to become biomarkers of severity and actors of defense. First, we studied whet...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/10/2178 |
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| author | Francis Schneider Raphaël Clère-Jehl Francesco Scavello Thierry Lavigne Angelo Corti Tommaso Angelone Youssef Haïkel Philippe Lavalle |
| author_facet | Francis Schneider Raphaël Clère-Jehl Francesco Scavello Thierry Lavigne Angelo Corti Tommaso Angelone Youssef Haïkel Philippe Lavalle |
| author_sort | Francis Schneider |
| collection | DOAJ |
| description | Life-threatening diseases challenge immunity with a release of chromogranins. This report focuses on Chromogranin A (CGA) and some of its derived peptides in critically ill patients, with attention paid to their potential to become biomarkers of severity and actors of defense. First, we studied whether circulating CGA may be a biomarker of outcome in non-selected critically ill patients: CGA concentrations were reliably associated with short-term death, systemic inflammation, and multiple organ failure. Additionally, when studying Vasostatin-I, the major N-terminal fragment of CGA, we noted its reliable prognostic value as early as admission if associated with age and lactate. In trauma patients, CGA concentrations heralded the occurrence of care-related infections. This was associated with an in vitro inhibitor impact of Chromofungin on both NF-kappa B- and API-transcriptional activities. Secondly, in life-threatening disease-induced oxidative stress, the multimerization of Vasostatin-I occurs with the loss of its anti-microbial properties ex vivo. In vivo, a 4%-concentration of non-oxidized albumin infusion reversed multimerization with a decrease in care-related infections. Finally, in vitro Catestatin impacted the polymorphonuclear cells-Ca++-dependent, calmodulin–regulated iPLA2 pathway by releasing immunity-related proteins. Furthermore, human Cateslytin, the active domain of Catestatin, helped destroy S. aureus: this prompted the creation of synthetic D-stereoisomer of CGA-derived peptides against superbugs for the protection of implanted devices. In conclusion, CGA consideration in the critically ill is only starting, but it offers interesting perspectives for improved outcomes. |
| first_indexed | 2024-03-09T19:34:18Z |
| format | Article |
| id | doaj.art-19f9ba5c72c6493398cf0d0a8c8afce3 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T19:34:18Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-19f9ba5c72c6493398cf0d0a8c8afce32023-11-24T01:57:38ZengMDPI AGPharmaceutics1999-49232022-10-011410217810.3390/pharmaceutics14102178Chromogranin A and Its Fragments in the Critically Ill: An Expanding Domain of Interest for Better CareFrancis Schneider0Raphaël Clère-Jehl1Francesco Scavello2Thierry Lavigne3Angelo Corti4Tommaso Angelone5Youssef Haïkel6Philippe Lavalle7Médecine Intensive—Réanimation, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Faculté de Médecine, FMTS at Unistra, 67085 Strasbourg, FranceMédecine Intensive—Réanimation, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Faculté de Médecine, FMTS at Unistra, 67085 Strasbourg, FranceBiomaterials and Bioengeneering, UMR_S1121, FMTS at Unistra, 67085 Strasbourg, FranceMédecine Intensive—Réanimation, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Faculté de Médecine, FMTS at Unistra, 67085 Strasbourg, FranceSan Raffaele Scientific Institute, Division of Experimental Oncology, Vita-Salute San Raffaele University, Via Olgettina 58, 20132 Milan, MI, ItalyLaboratory of Cellular and Molecular Cardiac Pathophysiology, Department of Biology, Ecology, and Earth Science, University of Calabria, 87036 Rende, CS, ItalyBiomaterials and Bioengeneering, UMR_S1121, FMTS at Unistra, 67085 Strasbourg, FranceBiomaterials and Bioengeneering, UMR_S1121, FMTS at Unistra, 67085 Strasbourg, FranceLife-threatening diseases challenge immunity with a release of chromogranins. This report focuses on Chromogranin A (CGA) and some of its derived peptides in critically ill patients, with attention paid to their potential to become biomarkers of severity and actors of defense. First, we studied whether circulating CGA may be a biomarker of outcome in non-selected critically ill patients: CGA concentrations were reliably associated with short-term death, systemic inflammation, and multiple organ failure. Additionally, when studying Vasostatin-I, the major N-terminal fragment of CGA, we noted its reliable prognostic value as early as admission if associated with age and lactate. In trauma patients, CGA concentrations heralded the occurrence of care-related infections. This was associated with an in vitro inhibitor impact of Chromofungin on both NF-kappa B- and API-transcriptional activities. Secondly, in life-threatening disease-induced oxidative stress, the multimerization of Vasostatin-I occurs with the loss of its anti-microbial properties ex vivo. In vivo, a 4%-concentration of non-oxidized albumin infusion reversed multimerization with a decrease in care-related infections. Finally, in vitro Catestatin impacted the polymorphonuclear cells-Ca++-dependent, calmodulin–regulated iPLA2 pathway by releasing immunity-related proteins. Furthermore, human Cateslytin, the active domain of Catestatin, helped destroy S. aureus: this prompted the creation of synthetic D-stereoisomer of CGA-derived peptides against superbugs for the protection of implanted devices. In conclusion, CGA consideration in the critically ill is only starting, but it offers interesting perspectives for improved outcomes.https://www.mdpi.com/1999-4923/14/10/2178albuminbiomaterialsCatestatinChromogranin AChromofungincritically ill |
| spellingShingle | Francis Schneider Raphaël Clère-Jehl Francesco Scavello Thierry Lavigne Angelo Corti Tommaso Angelone Youssef Haïkel Philippe Lavalle Chromogranin A and Its Fragments in the Critically Ill: An Expanding Domain of Interest for Better Care Pharmaceutics albumin biomaterials Catestatin Chromogranin A Chromofungin critically ill |
| title | Chromogranin A and Its Fragments in the Critically Ill: An Expanding Domain of Interest for Better Care |
| title_full | Chromogranin A and Its Fragments in the Critically Ill: An Expanding Domain of Interest for Better Care |
| title_fullStr | Chromogranin A and Its Fragments in the Critically Ill: An Expanding Domain of Interest for Better Care |
| title_full_unstemmed | Chromogranin A and Its Fragments in the Critically Ill: An Expanding Domain of Interest for Better Care |
| title_short | Chromogranin A and Its Fragments in the Critically Ill: An Expanding Domain of Interest for Better Care |
| title_sort | chromogranin a and its fragments in the critically ill an expanding domain of interest for better care |
| topic | albumin biomaterials Catestatin Chromogranin A Chromofungin critically ill |
| url | https://www.mdpi.com/1999-4923/14/10/2178 |
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