HIF1A inhibitor PX-478 reduces pathological stretch-induced calcification and collagen turnover in aortic valve

• DOI: 10.3389/fcvm.2022.1002067
• Publication Date: 2022-11-07T04:25:25Z
• Authors: Md Tausif Salim; Nicolas Villa-Roel; Booth Vogel; Hanjoong Jo; Ajit P. Yoganathan
• Keywords: HIF1A

HIF1A is significantly upregulated in calcified human aortic valves (AVs). Furthermore, inhibitor PX-478 was shown to inhibit AV calcification under static and disturbed flow conditions. Since elevated stretch one of the major mechanical stimuli for calcification, we investigated effect on collagen turnover a pathophysiological cyclic (15%) condition. Porcine valve (PAV) leaflets were cyclically (1 Hz) stretched at 15% 24 days osteogenic medium with or without PX-478. In addition, PAV physiological (10%) 3 regular assess its mRNA expression. It found that 100 μM (high concentration) could stretch, whereas 50 (moderate showed modest inhibitory calcification. Nonetheless, reduced stretch. Surprisingly, it observed (15% vs. 10%) did not have any significant expression leaflets. These results suggest may impart anti-calcific anti-matrix remodeling stretch-independent manner.