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Molecular genetics and genomics of heart failure

Nature Reviews Genetics volume 5, pages 811–825 (2004)Cite this article

Key Points

  • Heart failure is a multifactorial condition that is initiated by a broad range of events, both genetic and environmental

  • Heart failure might progress through a number of different molecular pathways, which are still poorly understood

  • In recent years, genomics has become prominent to the study of polygenic, multifactorial conditions

  • Microarray gene expression profiling studies have yielded useful preliminary data on the pathogenesis of heart failure and its precursors

  • The use of blood RNA, as opposed to tissue biopsy RNA, might represent an important step forward for genomic studies

Abstract

Heart failure is a major disease burden worldwide, and its incidence continues to increase as premature deaths from other cardiovascular conditions decline. Although the overall molecular portrait of this multifactorial disease remains incomplete, molecular and genetic studies have implicated, in recent decades, various pathways and genes that participate in the pathophysiology of heart failure. Here, we highlight the current understanding of the molecular and genetic basis of heart failure and show how recently developed genomic tools are providing a new perspective on this complex disease.

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Figure 1: Processes leading to various stages of heart failure.
Figure 2: Transmission of force and the structural network in the cardiomyocyte.

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Acknowledgements

The authors wish to thank Daniel Fefer, Isolde Prince, Jun Ma and Adam Dempsey for their help in researching and editing this manuscript. Genomic profiling work has been supported by grants from the National Institutes of Health

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Authors and Affiliations

  1. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Louis Pasteur Avenue, NRB room 0630K, Boston, 02115, Massachusetts, USA

    Choong-Chin Liew

  2. Duke University School of Medicine, Durham, 27708, North Carolina, USA

    Victor J. Dzau

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  1. Choong-Chin Liew
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  2. Victor J. Dzau
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Correspondence to Choong-Chin Liew or Victor J. Dzau.

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DATABASES

Entrez Protein

SERCA2

Entrez Gene

Tnf-α

OMIM

Brugada syndrome

long QT syndrome

FURTHER INFORMATION

Human Genome Project

Glossary

VENTRICULAR DYSFUNCTION

Condition in which the heart ventricles — the lower heart chambers — have lost function.

ACUTE MYOCARDIAL INFARCTION

Heart attack; the death of heart muscle caused by loss of blood supply to the muscle, normally a result of blocked coronary arteries.

DIASTOLIC

The phase of the cardiac cycle when ventricles are relaxed.

SYSTOLIC

The phase of the cardiac cycle when ventricles are contracted.

HYPERTROPHY

Enlargement of the cardiomyocyte characterized by an increased protein content.

CARDIOMYOCYTES

Muscle cells of the heart.

SARCOPLASMIC RETICULUM

Intracellular membranes of muscle cells that store and release calcium ions, triggering muscle contraction.

HAEMODYNAMIC STABILITY

Occurs when blood pressure is adequate to maintain organ function.

VASOCONSTRICTION

Blood vessel constriction.

AFTERLOAD

The tension necessary for muscle contraction.

VASODILATION

Blood vessel dilation.

NATRIURESIS

The presence of large amounts of sodium in the urine.

CACHECTIC

Wasting, malnutrition and loss of muscle mass caused by chronic disease.

CYTOKINES

Low mass, biologically active proteins that are secreted by cells of the immune system. They are signalling chemicals involved in various pathways that contribute to the inflammatory response.

MITRAL INSUFFICIENCY

Backflow of blood caused by improper closure of mitral valve — the valve that controls blood flow between the left atrium and left ventricle in the heart.

ISCHAEMIC CARDIOMYOPATHY

Heart muscle cell disease caused by lack of oxygen owing to blocked coronary arteries.

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Liew, CC., Dzau, V. Molecular genetics and genomics of heart failure. Nat Rev Genet 5, 811–825 (2004). https://doi.org/10.1038/nrg1470

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