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Role of integrins in mediating cardiac fibroblast–cardiomyocyte cross talk: a dynamic relationship in cardiac biology and pathophysiology

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Abstract

Integrins are a family of heterodimeric proteins expressed by cardiac fibroblasts and cardiomyocytes that provide critical adhesive and signaling functions through their interactions with the extracellular matrix (ECM) and the actin cytoskeleton. These adhesive processes are important for paracrine signaling, ECM homeostasis and for the intercellular interactions that impact cardiac cell biology and pathophysiological adaptation in disease. Despite considerable progress, our understanding of the interplay between cardiac cells, the ECM and integrins remains largely elusive. In this review, we examine the role of integrins in adhesive and signaling functions, and how these functions enable communication between cardiac fibroblasts, cardiomyocytes and the ECM. These processes strongly influence cardiac development and, later, the progression into cardiac disease. An improved understanding of this multi-dimensional system in cardiac tissues is needed to decipher the biological, spatiotemporal and mechanical cues that regulate cardiac health and the manifestation of cardiac disease. Greater insight into integrin function in cardiac tissues may also suggest new treatments for the prevention of heart failure.

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Abbreviations

Akt:

Protein kinase B

α-SMA:

α-Smooth muscle actin

ECM:

Extracellular matrix

ERK:

Extracellular-regulated kinase

DCM:

Diabetic cardiomyopathy

FAK:

Focal adhesion kinase

HBEGF:

Heparin-binding EGF-like growth factor

hiPSCs:

Human-induced pluripotent stem cells

MAPK:

Mitogen-activated protein kinases

MGO:

Methylglyoxal

MMPs:

Matrix metalloproteinases

PMCA4:

Plasma membrane calcium ATPase 4

RGD:

Arg-Gly-Asp

RhoA:

Ras homolog gene family, member A

TAC:

Transverse aortic constriction

TGF-β:

Transforming growth factor-β

WT:

Wild type

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Acknowledgements

This work was supported by an Ontario Heart and Stroke Foundation grant (NA-6736) to K.A.C and C.A.M, and (NA-7201) to K.A.C. C.A.M was supported by a Canada Research Chair in Matrix Dynamics. K.A.C. was supported by a CIHR New Investigator Award and an Early Researcher Award from the Ministry of Ontario.

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  1. Keenan Research Center for Biomedical Science, St. Michael’s Hospital and University of Toronto, Bond Wing 7-052, 30 Bond Street, Toronto, ON, M5B 1W8, Canada

    Robert A. Civitarese, Andras Kapus & Kim A. Connelly

  2. Matrix Dynamics Group, University of Toronto, Toronto, ON, Canada

    Christopher A. McCulloch

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  1. Robert A. Civitarese
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Correspondence to Kim A. Connelly.

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Civitarese, R.A., Kapus, A., McCulloch, C.A. et al. Role of integrins in mediating cardiac fibroblast–cardiomyocyte cross talk: a dynamic relationship in cardiac biology and pathophysiology. Basic Res Cardiol 112, 6 (2017). https://doi.org/10.1007/s00395-016-0598-6

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