Serum lipidomics meets cardiac magnetic resonance imaging: profiling of subjects at risk of dilated cardiomyopathy

Marko Sysi-Aho, Juha Koikkalainen, Tuulikki Seppänen-Laakso, Maija Kaartinen, Johanna Kuusisto, Keijo Peuhkurinen, Satu Kärkkäinen, Margareta Antila, Kirsi Lauerma, Eeva Reissell, Raija Jurkko, Jyrki Lötjönen, Tiina Heliö, Matej Oresic

Research output: Contribution to journalArticleScientificpeer-review

21 Citations (Scopus)

Abstract

Dilated cardiomyopathy (DCM), characterized by left ventricular dilatation and systolic dysfunction, constitutes a significant cause for heart failure, sudden cardiac death or need for heart transplantation. Lamin A/C gene (LMNA) on chromosome 1p12 is the most significant disease gene causing DCM and has been reported to cause 7-9% of DCM leading to cardiac transplantation. We have previously performed cardiac magnetic resonance imaging (MRI) to LMNA carriers to describe the early phenotype. Clinically, early recognition of subjects at risk of developing DCM would be important but is often difficult. Thus we have earlier used the MRI findings of these LMNA carriers for creating a model by which LMNA carriers could be identified from the controls at an asymptomatic stage. Some LMNA mutations may cause lipodystrophy. To characterize possible effects of LMNA mutations on lipid profile, we set out to apply global serum lipidomics using Ultra Performance Liquid Chromatography coupled to mass spectrometry in the same LMNA carriers, DCM patients without LMNA mutation and controls. All DCM patients, with or without LMNA mutation, differed from controls in regard to distinct serum lipidomic profile dominated by diminished odd-chain triglycerides and lipid ratios related to desaturation. Furthermore, we introduce a novel approach to identify associations between the molecular lipids from serum and the MR images from the LMNA carriers. The association analysis using dependency network and regression approaches also helped us to obtain novel insights into how the affected lipids might relate to cardiac shape and volume changes. Our study provides a framework for linking serum derived molecular markers not only with clinical endpoints, but also with the more subtle intermediate phenotypes, as derived from medical imaging, of potential pathophysiological relevance.
Original languageEnglish
Article numbere15744
Number of pages9
JournalPLoS ONE
Volume6
Issue number1
DOIs
Publication statusPublished - 2011
MoE publication typeA1 Journal article-refereed

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Lamin Type A
cardiomyopathy
Dilated Cardiomyopathy
Magnetic resonance
magnetic resonance imaging
Genes
Magnetic Resonance Imaging
Imaging techniques
Serum
genes
heart transplant
mutation
Lipids
Mutation
Heart Transplantation
lipids
Phenotype
Lipodystrophy
phenotype
ultra-performance liquid chromatography

Cite this

Sysi-Aho, Marko ; Koikkalainen, Juha ; Seppänen-Laakso, Tuulikki ; Kaartinen, Maija ; Kuusisto, Johanna ; Peuhkurinen, Keijo ; Kärkkäinen, Satu ; Antila, Margareta ; Lauerma, Kirsi ; Reissell, Eeva ; Jurkko, Raija ; Lötjönen, Jyrki ; Heliö, Tiina ; Oresic, Matej. / Serum lipidomics meets cardiac magnetic resonance imaging : profiling of subjects at risk of dilated cardiomyopathy. In: PLoS ONE. 2011 ; Vol. 6, No. 1.
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title = "Serum lipidomics meets cardiac magnetic resonance imaging: profiling of subjects at risk of dilated cardiomyopathy",
abstract = "Dilated cardiomyopathy (DCM), characterized by left ventricular dilatation and systolic dysfunction, constitutes a significant cause for heart failure, sudden cardiac death or need for heart transplantation. Lamin A/C gene (LMNA) on chromosome 1p12 is the most significant disease gene causing DCM and has been reported to cause 7-9{\%} of DCM leading to cardiac transplantation. We have previously performed cardiac magnetic resonance imaging (MRI) to LMNA carriers to describe the early phenotype. Clinically, early recognition of subjects at risk of developing DCM would be important but is often difficult. Thus we have earlier used the MRI findings of these LMNA carriers for creating a model by which LMNA carriers could be identified from the controls at an asymptomatic stage. Some LMNA mutations may cause lipodystrophy. To characterize possible effects of LMNA mutations on lipid profile, we set out to apply global serum lipidomics using Ultra Performance Liquid Chromatography coupled to mass spectrometry in the same LMNA carriers, DCM patients without LMNA mutation and controls. All DCM patients, with or without LMNA mutation, differed from controls in regard to distinct serum lipidomic profile dominated by diminished odd-chain triglycerides and lipid ratios related to desaturation. Furthermore, we introduce a novel approach to identify associations between the molecular lipids from serum and the MR images from the LMNA carriers. The association analysis using dependency network and regression approaches also helped us to obtain novel insights into how the affected lipids might relate to cardiac shape and volume changes. Our study provides a framework for linking serum derived molecular markers not only with clinical endpoints, but also with the more subtle intermediate phenotypes, as derived from medical imaging, of potential pathophysiological relevance.",
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Sysi-Aho, M, Koikkalainen, J, Seppänen-Laakso, T, Kaartinen, M, Kuusisto, J, Peuhkurinen, K, Kärkkäinen, S, Antila, M, Lauerma, K, Reissell, E, Jurkko, R, Lötjönen, J, Heliö, T & Oresic, M 2011, 'Serum lipidomics meets cardiac magnetic resonance imaging: profiling of subjects at risk of dilated cardiomyopathy', PLoS ONE, vol. 6, no. 1, e15744. https://doi.org/10.1371/journal.pone.0015744

Serum lipidomics meets cardiac magnetic resonance imaging : profiling of subjects at risk of dilated cardiomyopathy. / Sysi-Aho, Marko; Koikkalainen, Juha; Seppänen-Laakso, Tuulikki; Kaartinen, Maija; Kuusisto, Johanna; Peuhkurinen, Keijo; Kärkkäinen, Satu; Antila, Margareta; Lauerma, Kirsi; Reissell, Eeva; Jurkko, Raija; Lötjönen, Jyrki; Heliö, Tiina; Oresic, Matej.

In: PLoS ONE, Vol. 6, No. 1, e15744, 2011.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Serum lipidomics meets cardiac magnetic resonance imaging

T2 - profiling of subjects at risk of dilated cardiomyopathy

AU - Sysi-Aho, Marko

AU - Koikkalainen, Juha

AU - Seppänen-Laakso, Tuulikki

AU - Kaartinen, Maija

AU - Kuusisto, Johanna

AU - Peuhkurinen, Keijo

AU - Kärkkäinen, Satu

AU - Antila, Margareta

AU - Lauerma, Kirsi

AU - Reissell, Eeva

AU - Jurkko, Raija

AU - Lötjönen, Jyrki

AU - Heliö, Tiina

AU - Oresic, Matej

PY - 2011

Y1 - 2011

N2 - Dilated cardiomyopathy (DCM), characterized by left ventricular dilatation and systolic dysfunction, constitutes a significant cause for heart failure, sudden cardiac death or need for heart transplantation. Lamin A/C gene (LMNA) on chromosome 1p12 is the most significant disease gene causing DCM and has been reported to cause 7-9% of DCM leading to cardiac transplantation. We have previously performed cardiac magnetic resonance imaging (MRI) to LMNA carriers to describe the early phenotype. Clinically, early recognition of subjects at risk of developing DCM would be important but is often difficult. Thus we have earlier used the MRI findings of these LMNA carriers for creating a model by which LMNA carriers could be identified from the controls at an asymptomatic stage. Some LMNA mutations may cause lipodystrophy. To characterize possible effects of LMNA mutations on lipid profile, we set out to apply global serum lipidomics using Ultra Performance Liquid Chromatography coupled to mass spectrometry in the same LMNA carriers, DCM patients without LMNA mutation and controls. All DCM patients, with or without LMNA mutation, differed from controls in regard to distinct serum lipidomic profile dominated by diminished odd-chain triglycerides and lipid ratios related to desaturation. Furthermore, we introduce a novel approach to identify associations between the molecular lipids from serum and the MR images from the LMNA carriers. The association analysis using dependency network and regression approaches also helped us to obtain novel insights into how the affected lipids might relate to cardiac shape and volume changes. Our study provides a framework for linking serum derived molecular markers not only with clinical endpoints, but also with the more subtle intermediate phenotypes, as derived from medical imaging, of potential pathophysiological relevance.

AB - Dilated cardiomyopathy (DCM), characterized by left ventricular dilatation and systolic dysfunction, constitutes a significant cause for heart failure, sudden cardiac death or need for heart transplantation. Lamin A/C gene (LMNA) on chromosome 1p12 is the most significant disease gene causing DCM and has been reported to cause 7-9% of DCM leading to cardiac transplantation. We have previously performed cardiac magnetic resonance imaging (MRI) to LMNA carriers to describe the early phenotype. Clinically, early recognition of subjects at risk of developing DCM would be important but is often difficult. Thus we have earlier used the MRI findings of these LMNA carriers for creating a model by which LMNA carriers could be identified from the controls at an asymptomatic stage. Some LMNA mutations may cause lipodystrophy. To characterize possible effects of LMNA mutations on lipid profile, we set out to apply global serum lipidomics using Ultra Performance Liquid Chromatography coupled to mass spectrometry in the same LMNA carriers, DCM patients without LMNA mutation and controls. All DCM patients, with or without LMNA mutation, differed from controls in regard to distinct serum lipidomic profile dominated by diminished odd-chain triglycerides and lipid ratios related to desaturation. Furthermore, we introduce a novel approach to identify associations between the molecular lipids from serum and the MR images from the LMNA carriers. The association analysis using dependency network and regression approaches also helped us to obtain novel insights into how the affected lipids might relate to cardiac shape and volume changes. Our study provides a framework for linking serum derived molecular markers not only with clinical endpoints, but also with the more subtle intermediate phenotypes, as derived from medical imaging, of potential pathophysiological relevance.

U2 - 10.1371/journal.pone.0015744

DO - 10.1371/journal.pone.0015744

M3 - Article

VL - 6

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 1

M1 - e15744

ER -