RNA-sequencing analysis reveals new alterations in cardiomyocyte cytoskeletal genes in patients with heart failure.
Changes in cardiomyocyte cytoskeletal components, a crucial scaffold of cellular structure, have been found in heart failure (HF); however, the altered cytoskeletal network remains to be elucidated. This study investigated a new map of cytoskeleton-linked alterations that further explain the cardiomyocyte morphology and contraction disruption in HF. RNA-Sequencing (RNA-Seq) analysis was performed in 29 human LV tissue samples from ischemic cardiomyopathy (ICM; n=13) and dilated cardiomyopathy (DCM, n=10) patients undergoing cardiac transplantation and six healthy donors (control, CNT) and up to 16 ICM, 13 DCM and 7 CNT tissue samples for qRT-PCR. Gene Ontology analysis of RNA-Seq data demonstrated that cytoskeletal processes are altered in HF. We identified 60 differentially expressed cytoskeleton-related genes in ICM and 58 genes in DCM comparing with CNT, hierarchical clustering determined that shared cytoskeletal genes have a similar behavior in both pathologies. We further investigated MYLK4, RHOU, and ANKRD1 cytoskeletal components. qRT-PCR analysis revealed that MYLK4 was downregulated (-2.2-fold; P<0.05) and ANKRD1 was upregulated (2.3-fold; P<0.01) in ICM patients vs CNT. RHOU mRNA levels showed a statistical trend to decrease (-2.9-fold). In DCM vs CNT, MYLK4 (-4.0-fold; P<0.05) and RHOU (-3.9-fold; P<0.05) were downregulated and ANKRD1 (2.5-fold; P<0.05) was upregulated. Accordingly, MYLK4 and ANKRD1 protein levels were decreased and increased, respectively, in both diseases. Furthermore, ANKRD1 and RHOU mRNA levels were related with LV function (P<0.05). In summary, we have found a new map of changes in the ICM and DCM cardiomyocyte cytoskeleton. ANKRD1 and RHOU mRNA levels were related with LV function which emphasizes their relevance in HF. These new cytoskeletal changes may be responsible for altered contraction and cell architecture disruption in HF patients. Moreover, these results improve our knowledge on the role of cytoskeleton in functional and structural alterations in HF.
Cardiocirculatory Unit, IIS La Fe, Valencia, Spain.
Isabel
I
Herrer
Cardiocirculatory Unit, IIS La Fe, Valencia, Spain.
Esther
E
Roselló-Lletí
Cardiocirculatory Unit, IIS La Fe, Valencia, Spain.
Miguel
M
Rivera
Cardiocirculatory Unit, IIS La Fe, Valencia, Spain.
María Micaela
MM
Molina-Navarro
Cardiocirculatory Unit, IIS La Fe, Valencia, Spain.
Estefanía
E
Tarazón
Cardiocirculatory Unit, IIS La Fe, Valencia, Spain.
Ana
A
Ortega
Cardiocirculatory Unit, IIS La Fe, Hospital Universitario LA FE, Valencia, Spain.
Luis
L
Martínez-Dolz
Genomic System, Valencia, Spain.
Juan Carlos
JC
Triviño
Cardiology Unit, Hospital Clínico Santiago Compostela, La Coruña, Spain.
Francisca
F
Lago
Cardiology Unit, Hospital Clínico Santiago Compostela, La Coruña, Spain.
José R
JR
González-Juanatey
Cardiology Unit, Hospital Universitario San Juan, Alicante, Spain.
Vicente
V
Bertomeu
Cardiovascular Surgery Service, Hospital Universitario La Fe, Valencia, Spain.
José Anastasio
JA
Montero
Cardiocirculatory Unit, IIS La Fe, Valencia, Spain.
Manuel
0000000244157160
M
Portolés
D016022:Case-Control Studies; D016000:Cluster Analysis; D003599:Cytoskeleton / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006333:Heart Failure / Q000378:metabolism*; D006352:Heart Ventricles / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA; D015854:Up-Regulation
D012333:RNA, Messenger