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The possible role of the ubiquitin proteasome system in the development of atherosclerosis in diabetes

We have reviewed the impact of the ubiquitin proteasome system (UPS) on atherosclerosis progression of diabetic patients. A puzzle of many pieces of evidence suggests that UPS, in addition to its role in the removal of damaged proteins, is involved in a number of biological processes including infla...

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Autores principales: Marfella, Raffaele, D' Amico, Michele, Di Filippo, Clara, Siniscalchi, Mario, sasso, Ferdinando Carlo, Ferraraccio, Franca, Rossi, Francesco, Paolisso, Giuseppe
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2169213/
https://www.ncbi.nlm.nih.gov/pubmed/17971205
http://dx.doi.org/10.1186/1475-2840-6-35
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author Marfella, Raffaele
D' Amico, Michele
Di Filippo, Clara
Siniscalchi, Mario
sasso, Ferdinando Carlo
Ferraraccio, Franca
Rossi, Francesco
Paolisso, Giuseppe
author_facet Marfella, Raffaele
D' Amico, Michele
Di Filippo, Clara
Siniscalchi, Mario
sasso, Ferdinando Carlo
Ferraraccio, Franca
Rossi, Francesco
Paolisso, Giuseppe
author_sort Marfella, Raffaele
collection PubMed
description We have reviewed the impact of the ubiquitin proteasome system (UPS) on atherosclerosis progression of diabetic patients. A puzzle of many pieces of evidence suggests that UPS, in addition to its role in the removal of damaged proteins, is involved in a number of biological processes including inflammation, proliferation and apoptosis, all of which constitute important characteristics of atherosclerosis. From what can be gathered from the very few studies on the UPS in diabetic cardiovascular diseases published so far, the system seems to be functionally active to a different extent in the initiation, progression, and complication stage of atherosclerosis in the diabetic people. Further evidence for this theory, however, has to be given, for instance by specifically targeted antagonism of the UPS. Nonetheless, this hypothesis may help us understand why diverse therapeutic interventions, which have in common the ability to reduce ubiquitin-proteasome activity, can impede or delay the onset of diabetes and cardiovascular diseases (CVD). People with type 2 diabetes are disproportionately affected by CVD, compared with those without diabetes [1]. The prevalence, incidence, and mortality from all forms of CVD (myocardial infarction, cerebro-vascular disease and congestive heart failure) are strikingly increased in persons with diabetes compared with those withoutdiabetes [2]. Furthermore, diabetic patients have not benefited by the advances in the management of obesity, dyslipidemia, and hypertension that have resulted in a decrease in mortality for coronary heart disease (CHD) patients without diabetes [3]. Nevertheless, these risk factors do not fully explain the excess risk for CHD associated with diabetes [4,5]. Thus, the determinants of progression of atherosclerosis in persons with diabetes must be elucidated. Beyond the major risk factors, several studies have demonstrated that such factors, strictly related to diabetes, as insulin-resistance, post-prandial hyperglycemia and chronic hyperglycemia play a role in the atherosclerotic process and may require intervention [6,7]. Moreover, it is important to recognize that these risk factors frequently "cluster" inindividual patients and possibly interact with each other, favouring the atherosclerosis progression toward plaque instability. Thus, a fundamental question is, "which is the common soil hypothesis that may unifying the burden of all these factors on atherosclerosis of diabetic patients? Because evidences suggest that insulin-resistance, diabetes and CHD share in common a deregulation of ubiquitin-proteasome system (UPS), the major pathway for nonlysosomal intracellular protein degradation in eucaryotic cells [8,9], in this review ubiquitin-proteasome deregulation is proposed as the common persistent pathogenic factor mediating the initial stage of the atherosclerosis as well as the progression to complicated plaque in diabetic patients.
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spelling pubmed-21692132007-12-29 The possible role of the ubiquitin proteasome system in the development of atherosclerosis in diabetes Marfella, Raffaele D' Amico, Michele Di Filippo, Clara Siniscalchi, Mario sasso, Ferdinando Carlo Ferraraccio, Franca Rossi, Francesco Paolisso, Giuseppe Cardiovasc Diabetol Hypothesis We have reviewed the impact of the ubiquitin proteasome system (UPS) on atherosclerosis progression of diabetic patients. A puzzle of many pieces of evidence suggests that UPS, in addition to its role in the removal of damaged proteins, is involved in a number of biological processes including inflammation, proliferation and apoptosis, all of which constitute important characteristics of atherosclerosis. From what can be gathered from the very few studies on the UPS in diabetic cardiovascular diseases published so far, the system seems to be functionally active to a different extent in the initiation, progression, and complication stage of atherosclerosis in the diabetic people. Further evidence for this theory, however, has to be given, for instance by specifically targeted antagonism of the UPS. Nonetheless, this hypothesis may help us understand why diverse therapeutic interventions, which have in common the ability to reduce ubiquitin-proteasome activity, can impede or delay the onset of diabetes and cardiovascular diseases (CVD). People with type 2 diabetes are disproportionately affected by CVD, compared with those without diabetes [1]. The prevalence, incidence, and mortality from all forms of CVD (myocardial infarction, cerebro-vascular disease and congestive heart failure) are strikingly increased in persons with diabetes compared with those withoutdiabetes [2]. Furthermore, diabetic patients have not benefited by the advances in the management of obesity, dyslipidemia, and hypertension that have resulted in a decrease in mortality for coronary heart disease (CHD) patients without diabetes [3]. Nevertheless, these risk factors do not fully explain the excess risk for CHD associated with diabetes [4,5]. Thus, the determinants of progression of atherosclerosis in persons with diabetes must be elucidated. Beyond the major risk factors, several studies have demonstrated that such factors, strictly related to diabetes, as insulin-resistance, post-prandial hyperglycemia and chronic hyperglycemia play a role in the atherosclerotic process and may require intervention [6,7]. Moreover, it is important to recognize that these risk factors frequently "cluster" inindividual patients and possibly interact with each other, favouring the atherosclerosis progression toward plaque instability. Thus, a fundamental question is, "which is the common soil hypothesis that may unifying the burden of all these factors on atherosclerosis of diabetic patients? Because evidences suggest that insulin-resistance, diabetes and CHD share in common a deregulation of ubiquitin-proteasome system (UPS), the major pathway for nonlysosomal intracellular protein degradation in eucaryotic cells [8,9], in this review ubiquitin-proteasome deregulation is proposed as the common persistent pathogenic factor mediating the initial stage of the atherosclerosis as well as the progression to complicated plaque in diabetic patients. BioMed Central 2007-10-30 /pmc/articles/PMC2169213/ /pubmed/17971205 http://dx.doi.org/10.1186/1475-2840-6-35 Text en Copyright © 2007 Marfella et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Hypothesis
Marfella, Raffaele
D' Amico, Michele
Di Filippo, Clara
Siniscalchi, Mario
sasso, Ferdinando Carlo
Ferraraccio, Franca
Rossi, Francesco
Paolisso, Giuseppe
The possible role of the ubiquitin proteasome system in the development of atherosclerosis in diabetes
title The possible role of the ubiquitin proteasome system in the development of atherosclerosis in diabetes
title_full The possible role of the ubiquitin proteasome system in the development of atherosclerosis in diabetes
title_fullStr The possible role of the ubiquitin proteasome system in the development of atherosclerosis in diabetes
title_full_unstemmed The possible role of the ubiquitin proteasome system in the development of atherosclerosis in diabetes
title_short The possible role of the ubiquitin proteasome system in the development of atherosclerosis in diabetes
title_sort possible role of the ubiquitin proteasome system in the development of atherosclerosis in diabetes
topic Hypothesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2169213/
https://www.ncbi.nlm.nih.gov/pubmed/17971205
http://dx.doi.org/10.1186/1475-2840-6-35
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