Research priorities in sarcomeric cardiomyopathies
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Research priorities in sarcomeric cardiomyopathies. / van der Velden, Jolanda; Ho, Carolyn Y; Tardiff, Jil C; Olivotto, Iacopo; Knollmann, Bjorn C; Carrier, Lucie.
In: CARDIOVASC RES, Vol. 105, No. 4, 01.04.2015, p. 449-56.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Research priorities in sarcomeric cardiomyopathies
AU - van der Velden, Jolanda
AU - Ho, Carolyn Y
AU - Tardiff, Jil C
AU - Olivotto, Iacopo
AU - Knollmann, Bjorn C
AU - Carrier, Lucie
N1 - Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - The clinical variability in patients with sarcomeric cardiomyopathies is striking: a mutation causes cardiomyopathy in one individual, while the identical mutation is harmless in a family member. Moreover, the clinical phenotype varies ranging from asymmetric hypertrophy to severe dilatation of the heart. Identification of a single phenotype-associated disease mechanism would facilitate the design of targeted treatments for patient groups with different clinical phenotypes. However, evidence from both the clinic and basic knowledge of functional and structural properties of the sarcomere argues against a 'one size fits all' therapy for treatment of one clinical phenotype. Meticulous clinical and basic studies are needed to unravel the initial and progressive changes initiated by sarcomere mutations to better understand why mutations in the same gene can lead to such opposing phenotypes. Ultimately, we need to design an 'integrative physiology' approach to fully realize patient/gene-tailored therapy. Expertise within different research fields (cardiology, genetics, cellular biology, physiology, and pharmacology) must be joined to link longitudinal clinical studies with mechanistic insights obtained from molecular and functional studies in novel cardiac muscle systems. New animal models, which reflect both initial and more advanced stages of sarcomeric cardiomyopathy, will also aid in achieving these goals. Here, we discuss current priorities in clinical and preclinical investigation aimed at increasing our understanding of pathophysiological mechanisms leading from mutation to disease. Such information will provide the basis to improve risk stratification and to develop therapies to prevent/rescue cardiac dysfunction and remodelling caused by sarcomere mutations.
AB - The clinical variability in patients with sarcomeric cardiomyopathies is striking: a mutation causes cardiomyopathy in one individual, while the identical mutation is harmless in a family member. Moreover, the clinical phenotype varies ranging from asymmetric hypertrophy to severe dilatation of the heart. Identification of a single phenotype-associated disease mechanism would facilitate the design of targeted treatments for patient groups with different clinical phenotypes. However, evidence from both the clinic and basic knowledge of functional and structural properties of the sarcomere argues against a 'one size fits all' therapy for treatment of one clinical phenotype. Meticulous clinical and basic studies are needed to unravel the initial and progressive changes initiated by sarcomere mutations to better understand why mutations in the same gene can lead to such opposing phenotypes. Ultimately, we need to design an 'integrative physiology' approach to fully realize patient/gene-tailored therapy. Expertise within different research fields (cardiology, genetics, cellular biology, physiology, and pharmacology) must be joined to link longitudinal clinical studies with mechanistic insights obtained from molecular and functional studies in novel cardiac muscle systems. New animal models, which reflect both initial and more advanced stages of sarcomeric cardiomyopathy, will also aid in achieving these goals. Here, we discuss current priorities in clinical and preclinical investigation aimed at increasing our understanding of pathophysiological mechanisms leading from mutation to disease. Such information will provide the basis to improve risk stratification and to develop therapies to prevent/rescue cardiac dysfunction and remodelling caused by sarcomere mutations.
U2 - 10.1093/cvr/cvv019
DO - 10.1093/cvr/cvv019
M3 - SCORING: Journal article
C2 - 25631582
VL - 105
SP - 449
EP - 456
JO - CARDIOVASC RES
JF - CARDIOVASC RES
SN - 0008-6363
IS - 4
ER -