Identification of Genes and Pathways Regulated by Lamin A in Heart

Coste Pradas J.
Auguste G.
Matkovich S. J.
Lombardi R.
Chen S. N.
Garnett T.
Chamberlain K.
Riyad J. M.
Weber T.
Singh S. K.
Robertson M. J.
Coarfa C.
Marian A. J.
Gurha P.

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Publication date

January 2020

DOI

10.1161/JAHA.119.015690

Publisher

Ovid Technologies (Wolters Kluwer Health)

Language

English

Abstract

Background Mutations in the LMNA gene, encoding LMNA (lamin A/C), causes distinct disorders, including dilated cardiomyopathies, collectively referred to as laminopathies. The genes (coding and noncoding) and regulatory pathways controlled by LMNA in the heart are not completely defined. Methods and Results We analyzed cardiac transcriptome from wild-type, loss-of-function (Lmna-/-), and gain-of-function (Lmna-/- injected with adeno-associated virus serotype 9 expressing LMNA) mice with normal cardiac function. Deletion of Lmna (Lmna-/-) led to differential expression of 2193 coding and 629 long noncoding RNA genes in the heart (q<0.05). Re-expression of LMNA in the Lmna-/- mouse heart, completely rescued 501 coding and 208 non-coding and p...