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Crosstalk Between the Renin–Angiotensin System and the Advance Glycation End Product Axis in the Heart: Role of the Cardiac Fibroblast

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Abstract

Cardiac fibroblasts (CFs) are involved in maintaining extracellular matrix (ECM) homeostasis in the heart. CFs mediate responses to hormonal and mechanical stimuli and relay these to other local cell types through release of autocrine and/or paracrine factors. CFs also play important roles in the setting of injury, i.e., myocardial infarction, where ECM production is key to efficient scarring. However, conditions exist in which excess production of ECM by CFs can lead to cardiac fibrosis. Two important pathways known to be involved in development of cardiac fibrosis are renin–angiotensin system (RAS) and advanced glycation end products (AGE) receptor (RAGE) signaling cascades. This report summarizes actions of these two pathways on function of CFs. Because cardiac fibrosis is an important component of diabetic cardiomyopathy, we include new data that suggests a possible crosstalk between the RAS and AGE/RAGE pathway in order to activate CFs in diabetes.

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Acknowledgments

The authors are grateful to Dr. Laurence Brunton and Dr. Francisco Villarreal for help with experimental design and manuscript preparation. This work was supported by the American Heart Association Scientist Development Grant 10SDG2630130 and NH grants (1U54HK08460-01 and 8UL1TR000100-03 to A. C. Zambon). Postdoctoral support for K.G. Yamazaki was provided by the National Institute of General Medical Sciences Institutional Research and Academic Career (IRACDA) grant GM06852.

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Authors and Affiliations

  1. Department of Biological Sciences, California State University Los Angeles, 5151 State University Dr ASCL 312, Los Angeles, CA, USA

    Katrina Go Yamazaki & Eileen Gonzalez

  2. Department of Pharmacology, University of California, San Diego, La Jolla, CA, USA

    Alexander C. Zambon

  3. Department of Medicine, University of California, San Diego, La Jolla, CA, USA

    Alexander C. Zambon

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  1. Katrina Go Yamazaki
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  2. Eileen Gonzalez
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Correspondence to Katrina Go Yamazaki.

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Yamazaki, K.G., Gonzalez, E. & Zambon, A.C. Crosstalk Between the Renin–Angiotensin System and the Advance Glycation End Product Axis in the Heart: Role of the Cardiac Fibroblast. J. of Cardiovasc. Trans. Res. 5, 805–813 (2012). https://doi.org/10.1007/s12265-012-9405-4

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