Phosphate overload via the type III Na-dependent Pi transporter represses aortic wall elastic fiber formation

• Published in: Fujita Medical Journal 2024, Vol.10(4), pp.87-93
• Main Authors: Yoshino, Yasumasa, Hasegawa, Tomoka, Sugita, Shukei, Tomatsu, Eisuke, Murao, Naoya, Hiratsuka, Izumi, Sekiguchi-Ueda, Sahoko, Shibata, Megumi, Matsumoto, Takeo, Amizuka, Norio, Seino, Yusuke, Takayanagi, Takeshi, Sugimura, Yoshihisa, Suzuki, Atsushi
• Format: Article
• Language: English
• Subjects: Aorta; Atherosclerosis; Elastin; Fibrillin; Original; Phosphate
• ISSN: 2189-7247; 2189-7255; 2189-7255
• DOI: 10.20407/fmj.2023-004

Objectives: Phosphate (Pi) induces differentiation of arterial smooth muscle cells to the osteoblastic phenotype by inducing the type III Na-dependent Pi transporter Pit-1/solute carrier family member 1. This induction can contribute to arterial calcification, but precisely how Pi stress acts on the vascular wall remains unclear. We investigated the role of extracellular Pi in inducing microstructural changes in the arterial wall.Methods: Aortae of Pit-1-overexpressing transgenic (TG) rats and their wild-type (WT) littermates were obtained at 8 weeks after birth. The thoracic descending aorta from WT and TG rats was used for the measurement of wall thickness and uniaxial tensile testing. Structural and ultrastructural analyses were performed using light microscopy and transmission electron microscopy. Gene expression of connective tissue components in the aorta was quantified by quantitative real-time polymerase chain reaction.Results: Aortic wall thickness in TG rats was the same as that in WT rats. Uniaxial tensile testing showed that the circumferential breaking stress in TG rats was significantly lower than that in WT rats (p