Altered myocardial gene expression reveals possible maladaptive processes in heterozygous and homozygous cardiac myosin-binding protein C knockout mice.

L.M.T. Eijssen, B.J.C. van den Bosch, N. Vignier, P.J. Lindsey, C.M.M. van den Burg, L. Carrier, P.A.F.M. Doevendans, G.J. van der Vusse, H.J. Smeets

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Abstract

Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease characterized by left ventricular hypertrophy (LVH) predominantly affecting the interventricular septum. Cardiac myosin-binding protein C (cMyBP-C) mutations are common causes of FHC. Gene expression profiling was performed in left ventricles of 9-week-old wild-type mice, heterozygous cMyBP-C KO mice displaying asymmetric septal hypertrophy, and homozygous mice developing eccentric LVH. Knocking out one or two cMyBP-C genes leads primarily to gene expression changes indicating an increased energy demand, activation of the JNK and p38 parts of the MAPK pathway and deactivation of the ERK part, and induction of apoptosis. Altered gene expression for processes related to cardiac structure, contractile proteins, and protein turnover was also identified. Many of the changes were more pronounced in the homozygous KO mice. These alterations point to physiological and pathological adaptations in the prehypertrophic heterozygous KO mice and the hypertrophic homozygous mice.

Original languageEnglish
Pages (from-to)52-60
JournalGenomics
Volume91
Issue number1
DOIs
Publication statusPublished - 1 Jan 2008

Cite this

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title = "Altered myocardial gene expression reveals possible maladaptive processes in heterozygous and homozygous cardiac myosin-binding protein C knockout mice.",
abstract = "Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease characterized by left ventricular hypertrophy (LVH) predominantly affecting the interventricular septum. Cardiac myosin-binding protein C (cMyBP-C) mutations are common causes of FHC. Gene expression profiling was performed in left ventricles of 9-week-old wild-type mice, heterozygous cMyBP-C KO mice displaying asymmetric septal hypertrophy, and homozygous mice developing eccentric LVH. Knocking out one or two cMyBP-C genes leads primarily to gene expression changes indicating an increased energy demand, activation of the JNK and p38 parts of the MAPK pathway and deactivation of the ERK part, and induction of apoptosis. Altered gene expression for processes related to cardiac structure, contractile proteins, and protein turnover was also identified. Many of the changes were more pronounced in the homozygous KO mice. These alterations point to physiological and pathological adaptations in the prehypertrophic heterozygous KO mice and the hypertrophic homozygous mice.",
author = "L.M.T. Eijssen and {van den Bosch}, B.J.C. and N. Vignier and P.J. Lindsey and {van den Burg}, C.M.M. and L. Carrier and P.A.F.M. Doevendans and {van der Vusse}, G.J. and H.J. Smeets",
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language = "English",
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Altered myocardial gene expression reveals possible maladaptive processes in heterozygous and homozygous cardiac myosin-binding protein C knockout mice. / Eijssen, L.M.T.; van den Bosch, B.J.C.; Vignier, N.; Lindsey, P.J.; van den Burg, C.M.M.; Carrier, L.; Doevendans, P.A.F.M.; van der Vusse, G.J.; Smeets, H.J.

In: Genomics, Vol. 91, No. 1, 01.01.2008, p. 52-60.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Altered myocardial gene expression reveals possible maladaptive processes in heterozygous and homozygous cardiac myosin-binding protein C knockout mice.

AU - Eijssen, L.M.T.

AU - van den Bosch, B.J.C.

AU - Vignier, N.

AU - Lindsey, P.J.

AU - van den Burg, C.M.M.

AU - Carrier, L.

AU - Doevendans, P.A.F.M.

AU - van der Vusse, G.J.

AU - Smeets, H.J.

PY - 2008/1/1

Y1 - 2008/1/1

N2 - Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease characterized by left ventricular hypertrophy (LVH) predominantly affecting the interventricular septum. Cardiac myosin-binding protein C (cMyBP-C) mutations are common causes of FHC. Gene expression profiling was performed in left ventricles of 9-week-old wild-type mice, heterozygous cMyBP-C KO mice displaying asymmetric septal hypertrophy, and homozygous mice developing eccentric LVH. Knocking out one or two cMyBP-C genes leads primarily to gene expression changes indicating an increased energy demand, activation of the JNK and p38 parts of the MAPK pathway and deactivation of the ERK part, and induction of apoptosis. Altered gene expression for processes related to cardiac structure, contractile proteins, and protein turnover was also identified. Many of the changes were more pronounced in the homozygous KO mice. These alterations point to physiological and pathological adaptations in the prehypertrophic heterozygous KO mice and the hypertrophic homozygous mice.

AB - Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease characterized by left ventricular hypertrophy (LVH) predominantly affecting the interventricular septum. Cardiac myosin-binding protein C (cMyBP-C) mutations are common causes of FHC. Gene expression profiling was performed in left ventricles of 9-week-old wild-type mice, heterozygous cMyBP-C KO mice displaying asymmetric septal hypertrophy, and homozygous mice developing eccentric LVH. Knocking out one or two cMyBP-C genes leads primarily to gene expression changes indicating an increased energy demand, activation of the JNK and p38 parts of the MAPK pathway and deactivation of the ERK part, and induction of apoptosis. Altered gene expression for processes related to cardiac structure, contractile proteins, and protein turnover was also identified. Many of the changes were more pronounced in the homozygous KO mice. These alterations point to physiological and pathological adaptations in the prehypertrophic heterozygous KO mice and the hypertrophic homozygous mice.

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