Hypo-Osmotic Condition Accelerates Calcification of Extracellular Matrix in Cultured Vascular Smooth Muscle Cells
- Bone and Mineral Metabolism: Basic
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 501 Bone and Mineral Metabolism: Basic
- Matsueda, Shumei, Kyushu Daigaku Igakubu Daigakuin Igakukei Gakufu Daigakuin Igaku Kenkyuin, Fukuoka, Japan
- Yamada, Shunsuke, Kyushu Daigaku Byoin, Fukuoka, Japan
- Torisu, Kumiko, Kyushu Daigaku Igakubu Daigakuin Igakukei Gakufu Daigakuin Igaku Kenkyuin, Fukuoka, Japan
- Kitazono, Takanari, Kyushu Daigaku Igakubu Daigakuin Igakukei Gakufu Daigakuin Igaku Kenkyuin, Fukuoka, Japan
- Nakano, Toshiaki, Kyushu Daigaku Igakubu Daigakuin Igakukei Gakufu Daigakuin Igaku Kenkyuin, Fukuoka, Japan
Hyponatremia, one of the most frequently observed electrolyte disorders in patients with chronic kidney disease (CKD), is associated with increased mortality. Basic studies have shown that lower sodium levels or osmolar conditions in the culture media induce cell damages, oxidative stress, and apoptosis: the latter two are also shown to accelerate vascular calcification (VC), a critical complication in CKD patients. It is unknown whether hyponatremia or low osmolar condition plays roles in the pathogenesis of VC.
Human vascular smooth muscle cells (VSMCs) and dissected mouse aortic rings were cultured with calcifying medium, which was supplemented high calcium and phosphate. Sodium and other osmotic substances were further added to confirm their impact on VC and phenotypic changes of VSMCs. To determine the main signaling pathway of VC in relation to osmotic stress, we performed microarray analyses. Rac1-Akt pathway and sodium-calcium co-transporter (NCX1) were investigated. The effect of osmolarity on calciprotein particles formation (CPP) was also confirmed.
The lower osmolarity in the culture media exacerbated calcification of the extracellular matrix in cultured VSMCs as well as cultured mouse aortic rings. Conversely, the higher osmotic condition induced less calcification. Activation of Rac1-Akt signaling pathway, oxidative stress, CPP generation, and osteochondrogenic differentiation of VSMCs were identified as underlying mechanisms of VC acceleration mediated by low osmotic medium. Furthermore, sodium-dependent transcellular calcium efflux through NCX1 induced by high osmotic condition was proposed as mechanisms to prevent VC.
Our data suggest that a lower osmolarity including hyponatremic condition accelerates high-phosphate-induced VC by activating multiple cell-mediated processes and approach to avoid hypoosmotic condition would be important to prevent VC in CKD.