Maione, Angela Serena (2013) Study of Calcium-Calmodulin dependent kinases in the pathogenesis of the atherosclerotic plaque. [Tesi di dottorato]


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Tipologia del documento: Tesi di dottorato
Lingua: English
Titolo: Study of Calcium-Calmodulin dependent kinases in the pathogenesis of the atherosclerotic plaque
Maione, Angela
Data: 29 Marzo 2013
Numero di pagine: 44
Istituzione: Università degli Studi di Napoli Federico II
Dipartimento: Medicina Molecolare e Biotecnologie Mediche
Scuola di dottorato: Medicina molecolare
Dottorato: Patologia e fisiopatologia molecolare
Ciclo di dottorato: 25
Coordinatore del Corso di dottorato:
Avvedimento, Vittorio
Data: 29 Marzo 2013
Numero di pagine: 44
Parole chiave: Arteriosclerosis
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/04 - Patologia generale
Area 06 - Scienze mediche > MED/11 - Malattie dell'apparato cardiovascolare
Aree tematiche (7° programma Quadro): SALUTE e TUTELA DEL CONSUMATORE > Biotecnologie, strumenti e tecnologie generiche per la salute umana
Depositato il: 10 Apr 2013 13:30
Ultima modifica: 31 Dic 2016 02:00


Arteriosclerosis is a degenerative process that is physiological in aging but can be accelerated by number of risk factors, such as hypertension, diabetes, obesity, smoking, familial history. Healthy vessel walls harbour vascular smooth muscle cells, fibroblasts, endothelial cells, whereas in arteriosclerotic vessels inflammatory cells such as activated macrophages are also present. The biology of all these cells is tuned by calcium, that regulates both acute and adaptive, chronic events. Calcium signalling plays an important role in the regulation of cell proliferation through the crosstalk between multifunctional Calcium-Calmodulin dependent kinases (CaMKs) and a number of other signalling pathways, such as Erk. Nevertheless, how these cellular pathways interact with each other has yet to be investigated. Our recent studies demonstrate that a murine model lacking CaMKIV presents early onset arteriosclerosis, as well as increased CaMKII activity in selected cell types, thus implying a role for calcium signaling in the process. The recent genome-wide analysis of the Framingham Heart Study 100K Project shows an association between elevated diastolic blood pressure and the rs10491334 T/C Single Nucleotide Polymorphism of human CaMKIV gene. This finding suggests for this kinase, whose expression was once thought to be confined to the nervous tissue, a yet undisclosed role in vascular responses. We also obtained evidences of the existence of a crosstalk between CaMKII and CaMKIV, involved in the regulation of cell cycle progression. These results indicate a novel interplay between CaMKs, that has never been investigated in the modulation of cell proliferative responses, and might have tremendous implications in arteriosclerosis.

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