Research Paper Volume 11, Issue 12 pp 4125—4144
Altered FoxO1 and PPARγ interaction in age-related ER stress-induced hepatic steatosis
- 1 Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Korea
- 2 Department of Biopharmaceutical Engineering, Division of Chemistry and Biotechnology, Dongguk University, Gyeongju 38066, Korea
- 3 Department of Pediatrics, Children’s Hospital of Pittsburgh of UPMC, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15224, USA
- 4 Department of Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
Received: February 28, 2019 Accepted: June 17, 2019 Published: June 25, 2019https://doi.org/10.18632/aging.102042
How to Cite
Copyright: Kim et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Chronic kidney disease (CKD) is one of the most powerful predictors of premature cardiovascular disease (CVD), with heightened susceptibility to vascular intimal and medial calcification associated with a high cardiovascular mortality. Abnormal mineral metabolism of calcium (Ca) and phosphate (P) and underlying (dys)regulated hormonal control in CKD-mineral and bone disorder (MBD) is often accompanied by bone loss and increased vascular calcification (VC). While VC is known to be a multifactorial process and a major risk factor for CVD, the view of primary triggers and molecular mechanisms complexity has been shifting with novel scientific knowledge over the last years. In this review we highlight the importance of calcium-phosphate (CaP) mineral crystals in VC with an integrated view over the complexity of CKD, while discuss past and recent literature aiming to highlight novel horizons on this major health burden. Exacerbated VC in CKD patients might result from several interconnected mechanisms involving abnormal mineral metabolism, dysregulation of endogenous calcification inhibitors and inflammatory pathways, which function in a feedback loop driving disease progression and cardiovascular outcomes. We propose that novel approaches targeting simultaneously VC and inflammation might represent valuable new prognostic tools and targets for therapeutics and management of cardiovascular risk in the CKD population.