title: Mnk1 (Mitogen-Activated Protein Kinase-Interacting Kinase 1) Deficiency Aggravates Cardiac Remodeling in Mice.
abstract: Identifying the key factor involved in cardiac remodeling is critically important for developing novel strategies to protect against heart failure. Here, the role of Mnk1 (mitogen-activated protein kinase-interacting kinase 1) in cardiac remodeling was clarified. Cardiac remodeling was induced by transverse aortic constriction in Mnk1-knockout mice and their wild-type control mice. After 4 weeks of transverse aortic constriction, Mnk1-knockout mice developed exaggerated cardiac hypertrophy, fibrosis, dysfunction, and cardiomyocyte apoptosis and showed increased ERK1/2 (extracellular signal-regulated kinase 1/2) activation along with reduced sprouty2 expression. In line with the in vivo studies, Mnk1 knockdown by Mnk1 siRNA transfection induced exaggerated angiotensin II-induced cardiomyocyte hypertrophy in neonatal rat ventricular myocytes (NRVMs). Moreover, adenovirus-mediated overexpression of Mnk1 in NRVMs protected cardiomyocytes from angiotensin II-induced hypertrophy. In addition, overexpression of sprouty2 rescued NRVMs with Mnk1 knockdown from angiotensin II-induced hypertrophy. In accordance with the in vivo studies, as compared with the control group, Mnk1 knockdown led to hyperphosphorylation of ERK1/2 and suppression of the sprouty2 expression in angiotensin II-treated NRVMs; furthermore, Mnk1 overexpression led to hypophosphorylation of ERK1/2 in angiotensin II-treated NRVMs. In addition, sprouty2 overexpression suppressed the activation of ERK1/2 in angiotensin II-treated NRVMs with Mnk1 knockdown. Impressively, MnK1-knockout mice with overexpression of sprouty2 exhibited signs of a blunted cardiac hypertrophic response. Mnk1 likely carries out a suppressive function in cardiac hypertrophy via regulating the sprouty2/ERK1/2 pathway. It implicates Mnk1 in the development of cardiac remodeling.
authors.affiliation: From the Department of Cardiology, Renmin Hospital of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., H.L., Q.-Z.T.); and Cardiovascular Research Institute of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., X.-F.Z., S.-S.W., H.L., Q.-Z.T.).
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: From the Department of Cardiology, Renmin Hospital of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., H.L., Q.-Z.T.); and Cardiovascular Research Institute of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., X.-F.Z., S.-S.W., H.L., Q.-Z.T.).
authors.forename: Ling
authors.initials: L
authors.lastname: Yan
authors.affiliation: From the Department of Cardiology, Renmin Hospital of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., H.L., Q.-Z.T.); and Cardiovascular Research Institute of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., X.-F.Z., S.-S.W., H.L., Q.-Z.T.).
authors.forename: Qing-Qing
authors.initials: QQ
authors.lastname: Wu
authors.affiliation: From the Department of Cardiology, Renmin Hospital of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., H.L., Q.-Z.T.); and Cardiovascular Research Institute of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., X.-F.Z., S.-S.W., H.L., Q.-Z.T.).
authors.forename: Heng
authors.initials: H
authors.lastname: Zhou
authors.affiliation: From the Department of Cardiology, Renmin Hospital of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., H.L., Q.-Z.T.); and Cardiovascular Research Institute of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., X.-F.Z., S.-S.W., H.L., Q.-Z.T.).
authors.forename: Ya-Ge
authors.initials: YG
authors.lastname: Jin
authors.affiliation: From the Department of Cardiology, Renmin Hospital of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., H.L., Q.-Z.T.); and Cardiovascular Research Institute of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., X.-F.Z., S.-S.W., H.L., Q.-Z.T.).
authors.forename: Zhou-Yan
authors.initials: ZY
authors.lastname: Bian
authors.affiliation: From the Department of Cardiology, Renmin Hospital of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., H.L., Q.-Z.T.); and Cardiovascular Research Institute of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., X.-F.Z., S.-S.W., H.L., Q.-Z.T.).
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.affiliation: From the Department of Cardiology, Renmin Hospital of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., H.L., Q.-Z.T.); and Cardiovascular Research Institute of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., X.-F.Z., S.-S.W., H.L., Q.-Z.T.).
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yang
authors.affiliation: From the Department of Cardiology, Renmin Hospital of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., H.L., Q.-Z.T.); and Cardiovascular Research Institute of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., X.-F.Z., S.-S.W., H.L., Q.-Z.T.).
authors.forename: Di-Fei
authors.initials: DF
authors.lastname: Shen
authors.affiliation: From the Department of Cardiology, Renmin Hospital of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., H.L., Q.-Z.T.); and Cardiovascular Research Institute of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., X.-F.Z., S.-S.W., H.L., Q.-Z.T.).
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Zeng
authors.affiliation: From the Department of Cardiology, Renmin Hospital of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., H.L., Q.-Z.T.); and Cardiovascular Research Institute of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., X.-F.Z., S.-S.W., H.L., Q.-Z.T.).
authors.forename: Sha-Sha
authors.initials: SS
authors.lastname: Wang
authors.affiliation: From the Department of Cardiology, Renmin Hospital of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., H.L., Q.-Z.T.); and Cardiovascular Research Institute of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., X.-F.Z., S.-S.W., H.L., Q.-Z.T.).
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
authors.affiliation: From the Department of Cardiology, Renmin Hospital of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., H.L., Q.-Z.T.); and Cardiovascular Research Institute of Wuhan University, China (Y.Y., L.Y., Q.-Q.W., H.Z., Y.-G.J., Z.-Y.B., W.D., Z.Y., D.-F.S., X.-F.Z., S.-S.W., H.L., Q.-Z.T.). qztang@whu.edu.cn.
authors.forename: Qi-Zhu
authors.initials: QZ
authors.lastname: Tang
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism* / Q000503:physiopathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000172:deficiency / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011897:Random Allocation; D015398:Signal Transduction; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D015415:Biomarkers; D000804:Angiotensin II; C106281:Mknk1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases
keywords: Mnk1; apoptosis; cardiac hypertrophy; cardiomyocytes; fibrosis