| Abstract |
Various signaling pathways have been identified in the heart as important players during development, physiological adaptation or pathological processes. This includes the MAPK families, particularly p38MAPK, which is involved in several key cellular processes, including differentiation, proliferation, apoptosis, inflammation, metabolism and survival. Disrupted p38MAPK signaling has been associated with several diseases, including cardiovascular diseases (CVD) as well as diabetes and its related complications. Despite efforts to translate this knowledge into therapeutic avenues, p38 inhibitors have failed in clinical trials due to adverse effects. Inhibition of MK2, a downstream target of p38, appears to be a promising alternative strategy. Targeting MK2 activity may avoid the adverse effects linked to p38 inhibition, while maintaining its beneficial effects. MK2 was first considered as a therapeutic target in inflammatory diseases such as rheumatoid polyarthritis. A growing body of evidence now supports a key role of MK2 signaling in the pathogenesis of CVD, particularly ischemia/reperfusion injury, hypertrophy, and hypertension and that its inhibition or inactivation is associated with improved heart and vascular functions. More recently, MK2 was shown to be a potential player in diabetes and related complications, particularly in liver and heart, and perturbations in calcium handling and lipid metabolism. In this review, we will discuss recent advances in our knowledge of the role of MK2 in p38MAPK-mediated signaling and the benefits of its loss of function in CVD and diabetes, with an emphasis on the roles of MK2 in calcium handling and lipid metabolism. This article is part of a Special issue entitled Cardiac adaptations to obesity, diabetes and insulin resistance, edited by Professors Jan F.C. Glatz, Jason R.B. Dyck and Christine Des Rosiers.
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| MeSH term(s) |
Animals ; Calcium/metabolism ; Calcium Signaling/drug effects ; Cardiovascular Agents/therapeutic use ; Diabetic Cardiomyopathies/drug therapy ; Diabetic Cardiomyopathies/enzymology ; Diabetic Cardiomyopathies/pathology ; Diabetic Cardiomyopathies/physiopathology ; Energy Metabolism/drug effects ; Humans ; Intracellular Signaling Peptides and Proteins/antagonists & inhibitors ; Intracellular Signaling Peptides and Proteins/metabolism ; Lipid Metabolism/drug effects ; Molecular Targeted Therapy ; Myocytes, Cardiac/drug effects ; Myocytes, Cardiac/enzymology ; Myocytes, Cardiac/metabolism ; Protein Kinase Inhibitors/therapeutic use ; Protein-Serine-Threonine Kinases/antagonists & inhibitors ; Protein-Serine-Threonine Kinases/metabolism ; Signal Transduction/drug effects ; p38 Mitogen-Activated Protein Kinases/metabolism |
| Chemical Substances |
Cardiovascular Agents ; Intracellular Signaling Peptides and Proteins ; Protein Kinase Inhibitors ; MAP-kinase-activated kinase 2 (EC 2.7.1.-) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Calcium (SY7Q814VUP) |
| Language |
English |
| Publishing date |
2017-07-19 |
| Publishing country |
Netherlands |
| Document type |
Journal Article ; Research Support, Non-U.S. Gov't ; Review |
| ZDB-ID |
60-7 |
| ISSN |
1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0925-4439 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 1874-9399 |
| ISSN (online) |
1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 |
| ISSN |
0925-4439 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 1874-9399 |
| DOI |
10.1016/j.bbadis.2017.07.015 |
| Database |
MEDical Literature Analysis and Retrieval System OnLINE |
