To investigate whether insulin effect on endothelium is related to a specific signal transduction... more To investigate whether insulin effect on endothelium is related to a specific signal transduction pathway or reflects a more generalized action of the hormone, we studied in aortic rings of Wistar-Kyoto (WKY) rats the effects of the hormone on endothelium-dependent relaxations generated by acetylcholine, adenosine diphosphate, the selective α 2 -adrenergic agonist UK 14,304, and the calcium ionophore ionomycin. The responses were evaluated both in control conditions and after 30 minutes of exposure to three different levels of insulin (30, 100, and 500 μU/mL). Insulin failed to modify the phenylephrine aortic contractions and the relaxations induced by acetylcholine, adenosine diphosphate, and ionomycin. In contrast, both 100 and 500 μU/mL insulin were able to potentiate the UK 14,304–induced vasorelaxation (+96±19% and +91±12%, respectively). Pertussis toxin, which causes α 2 -adrenergic receptor G i uncoupling, reduced the α 2 -adrenergic vasorelaxation and prevented the insulin potentiation of the response to UK 14,304. Furthermore, in primary cultured aortic endothelial cells from WKY, we evaluated the conversion of [ 3 H]arginine to [ 3 H]citrulline in response to acetylcholine, ionomycin, and UK 14,304, both in control conditions and during insulin exposure. Again, insulin did not affect basal citrulline production or the increase induced by acetylcholine and ionomycin, whereas it potentiated the response to UK 14,304. Finally, in aortic rings of spontaneously hypertensive rats, insulin treatment (100 and 500 μU/mL) was unable to enhance the α 2 -adrenergic vasodilator response; in vascular endothelial cells from spontaneously hypertensive rats, insulin did not potentiate the increase in citrulline production evoked by UK 14,304. In conclusion, insulin selectively enhances α 2 -adrenergic endothelial vasorelaxation through a pertussis toxin–sensitive mechanism, by potentiating endothelial nitric oxide production. This vasorelaxant mechanism is altered in spontaneously hypertensive rats.
Objective: The functional contribution of non-myocyte cardiac cells, such as inflammatory cells, ... more Objective: The functional contribution of non-myocyte cardiac cells, such as inflammatory cells, in the setup of heart failure in response to doxorubicin (Dox) is recently becoming of growing interest. Objective: The study aims to evaluate the role of macrophages in cardiac damage elicited by Dox treatment. Design and method: C57BL/6 mice were treated with one intraperitoneal injection of Dox (20mg/Kg) and followed up for 5 days by cardiac ultrasounds (CUS), histological, and flow cytometry evaluations. We also tested the impact of Dox in macrophage-depleted mice. Murine cardiomyoblasts were directly treated with Dox (D-Dox) or with a conditioned medium from cultured murine macrophages treated with Dox (M-Dox). Results: In response to Dox, macrophage infiltration preceded cardiac damage. Macrophage depletion prevents Dox-induced damage, suggesting a key role of these cells in promoting cardiotoxicity. To evaluate the crosstalk between macrophages and cardiac cells in response to DOX...
International Journal of Environmental Research and Public Health
This article reports the study protocol of a nationwide multicentric study in seven Italian regio... more This article reports the study protocol of a nationwide multicentric study in seven Italian regions aimed at assessing the effectiveness of a digitally supported approach for the early screening of frailty risk factors in community-dwelling older adults. SUNFRAIL+ is a prospective observational cohort study aimed at carrying out a multidimensional assessment of community-dwelling older adults through an IT platform, which allows to connect the items of the SUNFRAIL frailty assessment tool with a cascading multidimensional in-depth assessment of the bio–psycho–social domains of frailty. Seven centers in seven Italian regions will administer the SUNFRAIL questionnaire to 100 older adults. According to the answers provided by older adults, they will be subjected to one or more validated in-depth scale tests in order to perform further diagnostic or dimensional evaluations. The study aims to contribute to the implementation and validation of a multiprofessional and multistakeholder serv...
GRK5 is a multifunctional protein that is able to move within the cell in response to various sti... more GRK5 is a multifunctional protein that is able to move within the cell in response to various stimuli to regulate key intracellular signaling from receptor activation, on plasmamembrane, to gene transcription, in the nucleus. Thus, GRK5 is involved in the development and progression of several pathological conditions including cancer. Several reports underline the involvement of GRK5 in the regulation of tumor growth even if they appear controversial. Indeed, depending on its subcellular localization and on the type of cancer, GRK5 is able to both inhibit cancer progression, through the desensitization of GPCR and non GPCR-receptors (TSH, PGE2R, PDGFR), and induce tumor growth, acting on non-receptor substrates (p53, AUKA and NPM1). All these findings suggest that targeting GRK5 could be an useful anti-cancer strategy, for specific tumor types. In this review, we will discuss the different effects of this kinase in the induction and progression of tumorigenesis, the molecular mechan...
This article describes how innovations are exploited in Campania (Italy) to improve health outcom... more This article describes how innovations are exploited in Campania (Italy) to improve health outcomes, quality of life, and sustainability of social and healthcare services. Campania's strategy for digitalization of health and care and for healthy aging is based on a person-centered, life-course, “One Health” approach, where demographic change is considered capable of stimulating a growth dynamic linked to the opportunities of combining the “Silver Economy” with local assets and the specific health needs of the population. The end-users (citizens, patients, and professionals) contribute to the co-creation of products and services, being involved in the identification of unmet needs and test-bed activity. The Campania Reference Site of the European Innovation Partnership on Active and Healthy Aging is a flexible regional ecosystem to address the challenge of an aging population with a life-course approach. The good practices, developed in the context of research and innovation proj...
The molecular mechanism underlying Cardiac hypertrophy involves, among others, abnormal intracell... more The molecular mechanism underlying Cardiac hypertrophy involves, among others, abnormal intracellular Ca++ dynamics. Ca++/Calmodulin protein kinase II (CaMKII) activation mediates Ca++ signaling in the hypertrophic transduction pathways. Nevertheless, the mechanism by which CaMKII integrates with other pathways is incompletely understood. We showed that phenylephrine (PE) induces cell proliferation through CaMKII and ERK complex formation, promoting phosphorylation and nuclear localization of both proteins. We hypothesize that the association with ERK, promotes nuclear localization in hypertrophic cardiomyocytes. In H9C2 cardiomyoblasts, PE induces both ERK and CaMKII activation and interaction which can both be reduced by the non selective CaMKs inhibitor KN93, by the selective CaMKII inhibitor AntCaNtide, and by the MEK/ERK inhibitor UO126. Next, we found that PE induces a time-dependent accumulation of both ERK and CaMKII into the nucleus, prevented by AnTCaNtide and UO126 pretre...
Although there is evidence of a growing awareness of the problem, no official policy statements o... more Although there is evidence of a growing awareness of the problem, no official policy statements or regulatory guidelines on polypharmacy have been released up to date by Italian Health Authorities. Medication review, application of appropriateness criteria and computerized prescription support systems are all possible approaches in order to improve the quality of prescribing in older persons. More focused training courses on multimorbidity and polytherapy management are encouraged. Furthermore a multidisciplinary approach integrating different health care professionals (physicians, pharmacists, and nurses) may positively impact on reducing the sense of fear related to discontinue or substitute drugs prescribed by others; the fragmentation of therapy among different specialists; reducing costs; and improving adverse drug reaction detection and reporting. Aiming at achieving the individualized pharmacotherapy, a multidisciplinary approach starting with identification of patients and r...
To investigate whether insulin effect on endothelium is related to a specific signal transduction... more To investigate whether insulin effect on endothelium is related to a specific signal transduction pathway or reflects a more generalized action of the hormone, we studied in aortic rings of Wistar-Kyoto (WKY) rats the effects of the hormone on endothelium-dependent relaxations generated by acetylcholine, adenosine diphosphate, the selective α 2 -adrenergic agonist UK 14,304, and the calcium ionophore ionomycin. The responses were evaluated both in control conditions and after 30 minutes of exposure to three different levels of insulin (30, 100, and 500 μU/mL). Insulin failed to modify the phenylephrine aortic contractions and the relaxations induced by acetylcholine, adenosine diphosphate, and ionomycin. In contrast, both 100 and 500 μU/mL insulin were able to potentiate the UK 14,304–induced vasorelaxation (+96±19% and +91±12%, respectively). Pertussis toxin, which causes α 2 -adrenergic receptor G i uncoupling, reduced the α 2 -adrenergic vasorelaxation and prevented the insulin potentiation of the response to UK 14,304. Furthermore, in primary cultured aortic endothelial cells from WKY, we evaluated the conversion of [ 3 H]arginine to [ 3 H]citrulline in response to acetylcholine, ionomycin, and UK 14,304, both in control conditions and during insulin exposure. Again, insulin did not affect basal citrulline production or the increase induced by acetylcholine and ionomycin, whereas it potentiated the response to UK 14,304. Finally, in aortic rings of spontaneously hypertensive rats, insulin treatment (100 and 500 μU/mL) was unable to enhance the α 2 -adrenergic vasodilator response; in vascular endothelial cells from spontaneously hypertensive rats, insulin did not potentiate the increase in citrulline production evoked by UK 14,304. In conclusion, insulin selectively enhances α 2 -adrenergic endothelial vasorelaxation through a pertussis toxin–sensitive mechanism, by potentiating endothelial nitric oxide production. This vasorelaxant mechanism is altered in spontaneously hypertensive rats.
Objective: The functional contribution of non-myocyte cardiac cells, such as inflammatory cells, ... more Objective: The functional contribution of non-myocyte cardiac cells, such as inflammatory cells, in the setup of heart failure in response to doxorubicin (Dox) is recently becoming of growing interest. Objective: The study aims to evaluate the role of macrophages in cardiac damage elicited by Dox treatment. Design and method: C57BL/6 mice were treated with one intraperitoneal injection of Dox (20mg/Kg) and followed up for 5 days by cardiac ultrasounds (CUS), histological, and flow cytometry evaluations. We also tested the impact of Dox in macrophage-depleted mice. Murine cardiomyoblasts were directly treated with Dox (D-Dox) or with a conditioned medium from cultured murine macrophages treated with Dox (M-Dox). Results: In response to Dox, macrophage infiltration preceded cardiac damage. Macrophage depletion prevents Dox-induced damage, suggesting a key role of these cells in promoting cardiotoxicity. To evaluate the crosstalk between macrophages and cardiac cells in response to DOX...
International Journal of Environmental Research and Public Health
This article reports the study protocol of a nationwide multicentric study in seven Italian regio... more This article reports the study protocol of a nationwide multicentric study in seven Italian regions aimed at assessing the effectiveness of a digitally supported approach for the early screening of frailty risk factors in community-dwelling older adults. SUNFRAIL+ is a prospective observational cohort study aimed at carrying out a multidimensional assessment of community-dwelling older adults through an IT platform, which allows to connect the items of the SUNFRAIL frailty assessment tool with a cascading multidimensional in-depth assessment of the bio–psycho–social domains of frailty. Seven centers in seven Italian regions will administer the SUNFRAIL questionnaire to 100 older adults. According to the answers provided by older adults, they will be subjected to one or more validated in-depth scale tests in order to perform further diagnostic or dimensional evaluations. The study aims to contribute to the implementation and validation of a multiprofessional and multistakeholder serv...
GRK5 is a multifunctional protein that is able to move within the cell in response to various sti... more GRK5 is a multifunctional protein that is able to move within the cell in response to various stimuli to regulate key intracellular signaling from receptor activation, on plasmamembrane, to gene transcription, in the nucleus. Thus, GRK5 is involved in the development and progression of several pathological conditions including cancer. Several reports underline the involvement of GRK5 in the regulation of tumor growth even if they appear controversial. Indeed, depending on its subcellular localization and on the type of cancer, GRK5 is able to both inhibit cancer progression, through the desensitization of GPCR and non GPCR-receptors (TSH, PGE2R, PDGFR), and induce tumor growth, acting on non-receptor substrates (p53, AUKA and NPM1). All these findings suggest that targeting GRK5 could be an useful anti-cancer strategy, for specific tumor types. In this review, we will discuss the different effects of this kinase in the induction and progression of tumorigenesis, the molecular mechan...
This article describes how innovations are exploited in Campania (Italy) to improve health outcom... more This article describes how innovations are exploited in Campania (Italy) to improve health outcomes, quality of life, and sustainability of social and healthcare services. Campania's strategy for digitalization of health and care and for healthy aging is based on a person-centered, life-course, “One Health” approach, where demographic change is considered capable of stimulating a growth dynamic linked to the opportunities of combining the “Silver Economy” with local assets and the specific health needs of the population. The end-users (citizens, patients, and professionals) contribute to the co-creation of products and services, being involved in the identification of unmet needs and test-bed activity. The Campania Reference Site of the European Innovation Partnership on Active and Healthy Aging is a flexible regional ecosystem to address the challenge of an aging population with a life-course approach. The good practices, developed in the context of research and innovation proj...
The molecular mechanism underlying Cardiac hypertrophy involves, among others, abnormal intracell... more The molecular mechanism underlying Cardiac hypertrophy involves, among others, abnormal intracellular Ca++ dynamics. Ca++/Calmodulin protein kinase II (CaMKII) activation mediates Ca++ signaling in the hypertrophic transduction pathways. Nevertheless, the mechanism by which CaMKII integrates with other pathways is incompletely understood. We showed that phenylephrine (PE) induces cell proliferation through CaMKII and ERK complex formation, promoting phosphorylation and nuclear localization of both proteins. We hypothesize that the association with ERK, promotes nuclear localization in hypertrophic cardiomyocytes. In H9C2 cardiomyoblasts, PE induces both ERK and CaMKII activation and interaction which can both be reduced by the non selective CaMKs inhibitor KN93, by the selective CaMKII inhibitor AntCaNtide, and by the MEK/ERK inhibitor UO126. Next, we found that PE induces a time-dependent accumulation of both ERK and CaMKII into the nucleus, prevented by AnTCaNtide and UO126 pretre...
Although there is evidence of a growing awareness of the problem, no official policy statements o... more Although there is evidence of a growing awareness of the problem, no official policy statements or regulatory guidelines on polypharmacy have been released up to date by Italian Health Authorities. Medication review, application of appropriateness criteria and computerized prescription support systems are all possible approaches in order to improve the quality of prescribing in older persons. More focused training courses on multimorbidity and polytherapy management are encouraged. Furthermore a multidisciplinary approach integrating different health care professionals (physicians, pharmacists, and nurses) may positively impact on reducing the sense of fear related to discontinue or substitute drugs prescribed by others; the fragmentation of therapy among different specialists; reducing costs; and improving adverse drug reaction detection and reporting. Aiming at achieving the individualized pharmacotherapy, a multidisciplinary approach starting with identification of patients and r...
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Papers by Guido Iaccarino