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Transforming growth factor beta signaling in adult cardiovascular diseases and repair

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Abstract

The majority of children with congenital heart disease now live into adulthood due to the remarkable surgical and medical advances that have taken place over the past half century. Because of this, adults now represent the largest age group with adult cardiovascular diseases. It includes patients with heart diseases that were not detected or not treated during childhood, those whose defects were surgically corrected but now need revision due to maladaptive responses to the procedure, those with exercise problems and those with age-related degenerative diseases. Because adult cardiovascular diseases in this population are relatively new, they are not well understood. It is therefore necessary to understand the molecular and physiological pathways involved if we are to improve treatments. Since there is a developmental basis to adult cardiovascular disease, transforming growth factor beta (TGFβ) signaling pathways that are essential for proper cardiovascular development may also play critical roles in the homeostatic, repair and stress response processes involved in adult cardiovascular diseases. Consequently, we have chosen to summarize the current information on a subset of TGFβ ligand and receptor genes and related effector genes that, when dysregulated, are known to lead to cardiovascular diseases and adult cardiovascular deficiencies and/or pathologies. A better understanding of the TGFβ signaling network in cardiovascular disease and repair will impact genetic and physiologic investigations of cardiovascular diseases in elderly patients and lead to an improvement in clinical interventions.

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Abbreviations

AOS:

Aortic aneurysms and dissections with early-onset osteoarthritis

ARVC/D or ARVD1:

Arrhythmogenic right ventricular cardiomyopathy/dysplasia

ATS:

Arterial Tortuosity syndrome

CCD:

Cleidocranial dysplasia

EDS:

Ehlers-Danlos syndrome

EMT:

Epithelial mesenchymal transition

HHT:

Hereditary hemorrhagic telangiectasia

JPS:

Juvenile polyposis syndrome

MFS:

Marfan syndrome

LDS:

Loeys-Dietz syndrome

TGFβNAb:

Pan-TGFβ neutralizing antibodies

XMVD:

X-linked myxomatous valvular dystrophy

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Acknowledgements

This work was supported, in part, by funds from the National Institutes of Health Grants – HL070174, HL92508, HL085708, HL077493, HL82851-03 and HL105280. Additional funding was provided by Arizona Biomedical Research Commission (ABRC #0901) and The Stephen Michael Schneider/The William J. "Billy" Gieszl Award.

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Authors and Affiliations

  1. BIO5 Institute, University of Arizona, Tucson, AZ, 85724, USA

    Thomas Doetschman & Mohamad Azhar

  2. Department of Cellular and Molecular Medicine, University of Arizona, 1656 E Mabel St, PO Box 245217, Tucson, AZ, 85724, USA

    Thomas Doetschman, Raymond B. Runyan & Mohamad Azhar

  3. Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, 37232-6600, USA

    Joey V. Barnett

  4. Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ, 85724, USA

    Todd D. Camenisch

  5. Steele Children’s Research Center, University of Arizona, Tucson, AZ, 85724, USA

    Todd D. Camenisch

  6. Southwest Environmental Health Sciences Center, University of Arizona, Tucson, AZ, 85724, USA

    Todd D. Camenisch

  7. Cancer Biology Graduate Interdisciplinary Program, and Department of Surgery, University of Arizona Health Sciences Center, 1501 North Campbell Avenue, Tucson, AZ, 85724, USA

    Ronald L. Heimark

  8. Molecular Cardiovascular Research Program, Sarver Heart Center, Department of Physiology, University of Arizona, Tucson, AZ, 85724, USA

    Henk L. Granzier

  9. Program in Developmental Biology and Neonatal Medicine, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Simon J. Conway

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  1. Thomas Doetschman
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  2. Joey V. Barnett
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  3. Raymond B. Runyan
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  8. Mohamad Azhar
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Correspondence to Mohamad Azhar.

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Doetschman, T., Barnett, J.V., Runyan, R.B. et al. Transforming growth factor beta signaling in adult cardiovascular diseases and repair. Cell Tissue Res 347, 203–223 (2012). https://doi.org/10.1007/s00441-011-1241-3

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  • DOI: https://doi.org/10.1007/s00441-011-1241-3

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