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Mechanisms of Synergistic Interactions of Diabetes and Hypertension in Chronic Kidney Disease: Role of Mitochondrial Dysfunction and ER Stress

  • Mechanisms of Hypertension and Target-Organ Damage (JE Hall and ME Hall, Section Editors)
  • Published:
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Abstract

Purpose of Review

To discuss the importance of synergistic interactions of diabetes mellitus (DM) and hypertension (HT) in causing chronic kidney disease and the potential molecular mechanisms involved.

Recent Findings

DM and HT are the two most important risk factors for chronic kidney disease (CKD) and development of end-stage renal disease (ESRD). The combination of HT and DM may synergistically promote the progression of renal injury through mechanisms that have not been fully elucidated. Hyperglycemia and other metabolic changes in DM initiate endoplasmic reticulum (ER) stress and mitochondrial (MT) adaptation in different types of glomerular cells. These adaptations appear to make the cells more vulnerable to HT-induced mechanical stress. Excessive activation of mechanosensors, possibly via transient receptor potential cation channel subfamily C member 6 (TRPC6), may lead to impaired calcium (Ca2+) homeostasis and further exacerbate ER stress and MT dysfunction promoting cellular apoptosis and glomerular injury.

Summary

The synergistic effects of HT and DM to promote kidney injury may be mediated by increased intraglomerular pressure. Chronic activation of mechanotransduction signaling may amplify metabolic effects of DM causing cellular injury through a vicious cycle of impaired Ca2+ homeostasis, mitochondrial dysfunction, and ER stress.

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Funding

The authors’ research was supported by the National Heart, Lung, and Blood Institute (P01 HL51971); National Institute of Diabetes and Digestive and Kidney Diseases (R00DK113280 and R01DK121411); and the National Institute of General Medical Sciences (P20 GM104357 and U54 GM115428) of the National Institutes of Health.

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  1. Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State St., Jackson, MS, 39216, USA

    Zhen Wang, Jussara M. do Carmo, Alexandre A. da Silva, Yiling Fu & John E. Hall

  2. Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson, MS, USA

    Zhen Wang, Jussara M. do Carmo, Alexandre A. da Silva, Yiling Fu & John E. Hall

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  1. Zhen Wang
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  2. Jussara M. do Carmo
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Correspondence to Zhen Wang.

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Wang, Z., do Carmo, J.M., da Silva, A.A. et al. Mechanisms of Synergistic Interactions of Diabetes and Hypertension in Chronic Kidney Disease: Role of Mitochondrial Dysfunction and ER Stress. Curr Hypertens Rep 22, 15 (2020). https://doi.org/10.1007/s11906-020-1016-x

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