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Mechanisms of Disease: intracrine physiology in the cardiovascular system

Abstract

The field of intracrine physiology attempts to codify the biological actions of intracrines—extracellular signaling proteins or peptides that also operate in the intracellular space, either because they are retained in their cells of synthesis or because they have been internalized by a target cell. Intracrines are structurally diverse; hormones, growth factors, DNA-binding proteins and enzymes can all display intracrine functionality. Here, we review the role of intracrines in the heart and vasculature, including the intracrine actions of renin–angiotensin-system components in cardiac pathology, dynorphin B in cardiac development, and a variety of factors in pathologic and therapeutic angiogenesis. We argue that principles of intracrine physiology can inform our understanding of important pathologic processes such as left ventricular hypertrophy, diabetic cardiomyopathy and arrythmogenesis, and can aid the development of more-effective therapeutic interventions in cardiovascular disease.

Key Points

  • The term 'intracrine' refers to the intracellular action of an extracellular signaling peptide

  • Intracrine factors are structurally diverse and include hormones, growth factors, DNA-binding proteins, enzymes, and other factors

  • Intracrines seem to form regulatory loops, which result in cell differentiation, altered hormonal responsiveness, and establishment of cellular memory

  • Recent results indicate that angiotensin II, renin and dynorphin can act in an intracrine fashion in cardiac myocytes

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Figure 1: The routes by which intracrines traffick are largely unknown and this is an area of ongoing research.

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Acknowledgements

This study was funded by the Ochsner Clinic Foundation and by National Heart, Lung, and Blood Institute grant HL072795.

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Correspondence to Richard N Re.

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Re, R., Cook, J. Mechanisms of Disease: intracrine physiology in the cardiovascular system. Nat Rev Cardiol 4, 549–557 (2007). https://doi.org/10.1038/ncpcardio0985

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