CRISPLD1: a novel conserved target in the transition to human heart failure

Basic Research in Cardiology
Sara KhadjehGerd Hasenfuss

Abstract

Heart failure is a major health problem worldwide with a significant morbidity and mortality rate. Although studied extensively in animal models, data from patients at the compensated disease stage are lacking. We sampled myocardium biopsies from aortic stenosis patients with compensated hypertrophy and moderate heart failure and used transcriptomics to study the transition to failure. Sequencing and comparative analysis of analogous samples of mice with transverse aortic constriction identified 25 candidate genes with similar regulation in response to pressure overload, reflecting highly conserved molecular processes. The gene cysteine-rich secretory protein LCCL domain containing 1 (CRISPLD1) is upregulated in the transition to failure in human and mouse and its function is unknown. Homology to ion channel regulatory toxins suggests a role in Ca2+ cycling. CRISPR/Cas9-mediated loss-of-function leads to dysregulated Ca2+ handling in human-induced pluripotent stem cell-derived cardiomyocytes. The downregulation of prohypertrophic, proapoptotic and Ca2+-signaling pathways upon CRISPLD1-KO and its upregulation in the transition to failure implicates a contribution to adverse remodeling. These findings provide new pathophysiologic...Continue Reading

References

Jan 11, 1990·The New England Journal of Medicine·A M Katz
Apr 1, 1994·The Journal of Membrane Biology·M NobileG Prestipino
Jan 1, 1993·Advances in Experimental Medicine and Biology·G HasenfussH Just
Jun 1, 1996·Experimental Brain Research·M NobileL D Possani
Feb 22, 2001·Annual Review of Physiology·J D Molkentin, G W Dorn
Mar 7, 2001·American Heart Journal·B A VakiliR B Devereux
Nov 14, 2002·Physiological Genomics·M SteenmanJ J Léger
Jan 14, 2003·Annual Review of Physiology·N Frey, E N Olson
May 10, 2003·American Journal of Physiology. Heart and Circulatory Physiology·Ping HuSheldon E Litwin
Mar 1, 2005·Journal of Molecular and Cellular Cardiology·Umesh C SharmaJos G Maessen
Apr 6, 2006·The Journal of Clinical Investigation·Timothy D O'ConnellPaul C Simpson
Jun 5, 2007·Pharmacotherapy·Jaekyu Shin, Julie A Johnson
Jul 4, 2007·Circulation·Thomas ThumJohann Bauersachs
Jul 11, 2007·Circulation·Dariush MozaffarianWayne C Levy
Jul 3, 2008·The Annals of Pharmacotherapy·Simon de DenusMichel White
Jul 17, 2008·Comparative and Functional Genomics·Claes C StrømSøren P Sheikh
Sep 11, 2008·Physiological Genomics·Uri David Akavia, Dafna Benayahu
Feb 10, 2009·Journal of Proteome Research·Mireya Gonzalez-BegneJohn R Yates
Jun 26, 2009·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Dominique BalharryKelly A Bérubé
Jul 30, 2009·Circulation Journal : Official Journal of the Japanese Circulation Society·Masanori Asakura, Masafumi Kitakaze
Mar 10, 2010·Disease Models & Mechanisms·Ross Breckenridge
Jan 22, 2011·Birth Defects Research. Part A, Clinical and Molecular Teratology·Brett T ChiquetJacqueline T Hecht
Aug 11, 2011·Circulation. Cardiovascular Genetics·Andreas S BarthGordon F Tomaselli
Mar 27, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Melody P LunMaria K Lehtinen
Feb 18, 2016·The Journal of Experimental Medicine·Per HolmfeldtShannon McKinney-Freeman
Jul 2, 2016·Journal of Clinical Medicine·Arati A Inamdar, Ajinkya C Inamdar
Sep 1, 2014·ESC Heart Failure·Piotr PonikowskiGerasimos Filippatos
Nov 11, 2017·Gene Expression Patterns : GEP·Yong WanHeather L Szabo-Rogers
Mar 27, 2018·Journal of the American Heart Association·Ibrahim El-BattrawyIbrahim Akin
Apr 28, 2018·Pharmacogenomics·Simon de DenusUNKNOWN CANDIID II investigators

❮ Previous
Next ❯

Citations

May 25, 2021·Frontiers in Cardiovascular Medicine·Michele CorrealeNatale Daniele Brunetti

❮ Previous
Next ❯

Methods Mentioned

BETA
RNA-seq
Biopsy
nucleotide exchange
exome sequencing
biopsies
dissection
flow cytometry
transfection
fluorescence activated cell sorting
electrophoresis

Software Mentioned

ImageJ
LabChart Pro
BaseCaller
SAMtools
excel
DESeq2
R
Bioconductor
HTSeq
CASAVA

Related Concepts

Related Feeds

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.

Cardiovascular Homeostasis

Cardiovascular regulation and homeostasis is important in maintaining health and dysfunction may lead to cardiovascular diseases. Nitric oxide and vascular endothelium are one of many molecules involved in the homeostatic mechanism. Here is the latest research on cardiovascular homeostasis.

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.