Cargando…

Camk2n1 Is a Negative Regulator of Blood Pressure, Left Ventricular Mass, Insulin Sensitivity, and Promotes Adiposity

Metabolic syndrome is a cause of coronary artery disease and type 2 diabetes mellitus. Camk2n1 resides in genomic loci for blood pressure, left ventricle mass, and type 2 diabetes mellitus, and in the spontaneously hypertensive rat model of metabolic syndrome, Camk2n1 expression is cis-regulated in...

Descripción completa

Detalles Bibliográficos
Autores principales: Alfazema, Neza, Barrier, Marjorie, de Procé, Sophie Marion, Menzies, Robert I., Carter, Roderick, Stewart, Kevin, Diaz, Ana Garcia, Moyon, Ben, Webster, Zoe, Bellamy, Christopher O.C., Arends, Mark J., Stimson, Roland H., Morton, Nicholas M., Aitman, Timothy J., Coan, Philip M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott, Williams & Wilkins 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6686962/
https://www.ncbi.nlm.nih.gov/pubmed/31327268
http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.12409
_version_ 1783442650663223296
author Alfazema, Neza
Barrier, Marjorie
de Procé, Sophie Marion
Menzies, Robert I.
Carter, Roderick
Stewart, Kevin
Diaz, Ana Garcia
Moyon, Ben
Webster, Zoe
Bellamy, Christopher O.C.
Arends, Mark J.
Stimson, Roland H.
Morton, Nicholas M.
Aitman, Timothy J.
Coan, Philip M.
author_facet Alfazema, Neza
Barrier, Marjorie
de Procé, Sophie Marion
Menzies, Robert I.
Carter, Roderick
Stewart, Kevin
Diaz, Ana Garcia
Moyon, Ben
Webster, Zoe
Bellamy, Christopher O.C.
Arends, Mark J.
Stimson, Roland H.
Morton, Nicholas M.
Aitman, Timothy J.
Coan, Philip M.
author_sort Alfazema, Neza
collection PubMed
description Metabolic syndrome is a cause of coronary artery disease and type 2 diabetes mellitus. Camk2n1 resides in genomic loci for blood pressure, left ventricle mass, and type 2 diabetes mellitus, and in the spontaneously hypertensive rat model of metabolic syndrome, Camk2n1 expression is cis-regulated in left ventricle and fat and positively correlates with adiposity. Therefore, we knocked out Camk2n1 in spontaneously hypertensive rat to investigate its role in metabolic syndrome. Compared with spontaneously hypertensive rat, Camk2n1(−/−) rats had reduced cardiorenal CaMKII (Ca(2+)/calmodulin-dependent kinase II) activity, lower blood pressure, enhanced nitric oxide bioavailability, and reduced left ventricle mass associated with altered hypertrophic networks. Camk2n1 deficiency reduced insulin resistance, visceral fat, and adipogenic capacity through the altered cell cycle and complement pathways, independent of CaMKII. In human visceral fat, CAMK2N1 expression correlated with adiposity and genomic variants that increase CAMK2N1 expression associated with increased risk of coronary artery disease and type 2 diabetes mellitus. Camk2n1 regulates multiple networks that control metabolic syndrome traits and merits further investigation as a therapeutic target in humans.
format Online
Article
Text
id pubmed-6686962
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Lippincott, Williams & Wilkins
record_format MEDLINE/PubMed
spelling pubmed-66869622019-09-16 Camk2n1 Is a Negative Regulator of Blood Pressure, Left Ventricular Mass, Insulin Sensitivity, and Promotes Adiposity Alfazema, Neza Barrier, Marjorie de Procé, Sophie Marion Menzies, Robert I. Carter, Roderick Stewart, Kevin Diaz, Ana Garcia Moyon, Ben Webster, Zoe Bellamy, Christopher O.C. Arends, Mark J. Stimson, Roland H. Morton, Nicholas M. Aitman, Timothy J. Coan, Philip M. Hypertension Original Articles Metabolic syndrome is a cause of coronary artery disease and type 2 diabetes mellitus. Camk2n1 resides in genomic loci for blood pressure, left ventricle mass, and type 2 diabetes mellitus, and in the spontaneously hypertensive rat model of metabolic syndrome, Camk2n1 expression is cis-regulated in left ventricle and fat and positively correlates with adiposity. Therefore, we knocked out Camk2n1 in spontaneously hypertensive rat to investigate its role in metabolic syndrome. Compared with spontaneously hypertensive rat, Camk2n1(−/−) rats had reduced cardiorenal CaMKII (Ca(2+)/calmodulin-dependent kinase II) activity, lower blood pressure, enhanced nitric oxide bioavailability, and reduced left ventricle mass associated with altered hypertrophic networks. Camk2n1 deficiency reduced insulin resistance, visceral fat, and adipogenic capacity through the altered cell cycle and complement pathways, independent of CaMKII. In human visceral fat, CAMK2N1 expression correlated with adiposity and genomic variants that increase CAMK2N1 expression associated with increased risk of coronary artery disease and type 2 diabetes mellitus. Camk2n1 regulates multiple networks that control metabolic syndrome traits and merits further investigation as a therapeutic target in humans. Lippincott, Williams & Wilkins 2019-09 2019-07-22 /pmc/articles/PMC6686962/ /pubmed/31327268 http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.12409 Text en © 2019 The Authors. Hypertension is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.
spellingShingle Original Articles
Alfazema, Neza
Barrier, Marjorie
de Procé, Sophie Marion
Menzies, Robert I.
Carter, Roderick
Stewart, Kevin
Diaz, Ana Garcia
Moyon, Ben
Webster, Zoe
Bellamy, Christopher O.C.
Arends, Mark J.
Stimson, Roland H.
Morton, Nicholas M.
Aitman, Timothy J.
Coan, Philip M.
Camk2n1 Is a Negative Regulator of Blood Pressure, Left Ventricular Mass, Insulin Sensitivity, and Promotes Adiposity
title Camk2n1 Is a Negative Regulator of Blood Pressure, Left Ventricular Mass, Insulin Sensitivity, and Promotes Adiposity
title_full Camk2n1 Is a Negative Regulator of Blood Pressure, Left Ventricular Mass, Insulin Sensitivity, and Promotes Adiposity
title_fullStr Camk2n1 Is a Negative Regulator of Blood Pressure, Left Ventricular Mass, Insulin Sensitivity, and Promotes Adiposity
title_full_unstemmed Camk2n1 Is a Negative Regulator of Blood Pressure, Left Ventricular Mass, Insulin Sensitivity, and Promotes Adiposity
title_short Camk2n1 Is a Negative Regulator of Blood Pressure, Left Ventricular Mass, Insulin Sensitivity, and Promotes Adiposity
title_sort camk2n1 is a negative regulator of blood pressure, left ventricular mass, insulin sensitivity, and promotes adiposity
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6686962/
https://www.ncbi.nlm.nih.gov/pubmed/31327268
http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.12409
work_keys_str_mv AT alfazemaneza camk2n1isanegativeregulatorofbloodpressureleftventricularmassinsulinsensitivityandpromotesadiposity
AT barriermarjorie camk2n1isanegativeregulatorofbloodpressureleftventricularmassinsulinsensitivityandpromotesadiposity
AT deprocesophiemarion camk2n1isanegativeregulatorofbloodpressureleftventricularmassinsulinsensitivityandpromotesadiposity
AT menziesroberti camk2n1isanegativeregulatorofbloodpressureleftventricularmassinsulinsensitivityandpromotesadiposity
AT carterroderick camk2n1isanegativeregulatorofbloodpressureleftventricularmassinsulinsensitivityandpromotesadiposity
AT stewartkevin camk2n1isanegativeregulatorofbloodpressureleftventricularmassinsulinsensitivityandpromotesadiposity
AT diazanagarcia camk2n1isanegativeregulatorofbloodpressureleftventricularmassinsulinsensitivityandpromotesadiposity
AT moyonben camk2n1isanegativeregulatorofbloodpressureleftventricularmassinsulinsensitivityandpromotesadiposity
AT websterzoe camk2n1isanegativeregulatorofbloodpressureleftventricularmassinsulinsensitivityandpromotesadiposity
AT bellamychristopheroc camk2n1isanegativeregulatorofbloodpressureleftventricularmassinsulinsensitivityandpromotesadiposity
AT arendsmarkj camk2n1isanegativeregulatorofbloodpressureleftventricularmassinsulinsensitivityandpromotesadiposity
AT stimsonrolandh camk2n1isanegativeregulatorofbloodpressureleftventricularmassinsulinsensitivityandpromotesadiposity
AT mortonnicholasm camk2n1isanegativeregulatorofbloodpressureleftventricularmassinsulinsensitivityandpromotesadiposity
AT aitmantimothyj camk2n1isanegativeregulatorofbloodpressureleftventricularmassinsulinsensitivityandpromotesadiposity
AT coanphilipm camk2n1isanegativeregulatorofbloodpressureleftventricularmassinsulinsensitivityandpromotesadiposity