Herum KM, Romaine A, Wang A, et al. - Given cases with hypertension or valvular stenosis exhibit pressure overload of the heart, which leads to cardiac fibrosis due to excessive generation of extracellular matrix by activated cardiac fibroblasts, researchers focused on the influence of thrombin-cleaved osteopontin on fibrosis in the heart, as well as looked at the role of syndecan-4 in regulating cleavage of osteopontin. In the pressure-overloaded heart of mice subjected to aortic banding, upregulation of osteopontin happened as well as it was cleaved by thrombin. Plasma samples from patients with aortic stenosis taking crystalloid exhibited higher cleaved osteopontin vs blood cardioplegia, possibly due to less heparin-induced inhibition of thrombin. Overall, findings revealed that collagen generation by cardiac fibroblasts was induced by thrombin-cleaved osteopontin. Although thrombin-induced osteopontin cleavage was prevented by syndecan-4, this protective effect vanished when syndecan-4 was shed in later phases of remodeling, aiding to cardiac fibrosis progression.