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Pathological cardiac hypertrophy: the synergy of adenylyl cyclases inhibition in cardiac and immune cells during chronic catecholamine stress

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Abstract

Response to stressors in our environment and daily lives is an adaptation conserved through evolution as it is beneficial in enhancing the survival and continuity of humans. Although stressors have evolved, the drastic physiological response they elicit still remains unchanged. The chronic secretion and circulation of catecholamines to produce physical responses when they are not required may result in pathological consequences which affect cardiac function drastically. This review seeks to point out the probable implication of chronic stress in inducing an inflammation disorder in the heart. We discussed the likely synergy of a G protein-independent stimuli signaling via β2-adrenergic receptors in both cardiomyocytes and immune cells during chronic catecholamine stress. To explain this synergy, we hypothesized the possibility of adenylyl cyclases having a regulatory effect on G protein-coupled receptor kinases. This was based on the negative correlations they exhibit during normal cardiac function and heart failures. As such, the downregulation of adenylyl cyclases in cardiomyocytes and immune cells during chronic catecholamine stress enhances the expressions of G protein-coupled receptor kinases. In addition, we explain the maladaptive roles played by G protein-coupled receptor kinase and extracellular signal-regulated kinase in the synergistic cascade that pathologically remodels the heart. Finally, we highlighted the therapeutic potentials of an adenylyl cyclases stimulator to attenuate pathological cardiac hypertrophy (PCH) and improve cardiac function in patients developing cardiac disorders due to chronic catecholamine stress.

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Acknowledgements

We acknowledge the invaluable help of Dr. Ruqayya Rizvi and Dr. Seyram Yao Adzraku for proofreading the entire manuscript.

Funding

This work was supported by grants from the National Natural Science Foundation of China (No.81370329, No.81461138036), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX17-1712).

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  1. Department of Physiology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, Jiangsu, China

    Gabriel Komla Adzika, Jeremiah Ong’achwa Machuki, Wenkang Shang, Hongjian Hou, Tongtong Ma, Lijuan Wu, Juan Geng, Xide Hu, Xianluo Ma & Hong Sun

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  1. Gabriel Komla Adzika
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  2. Jeremiah Ong’achwa Machuki
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Adzika, G.K., Machuki, J.O., Shang, W. et al. Pathological cardiac hypertrophy: the synergy of adenylyl cyclases inhibition in cardiac and immune cells during chronic catecholamine stress. J Mol Med 97, 897–907 (2019). https://doi.org/10.1007/s00109-019-01790-0

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