A Lindera obtusiloba Extract Blocks Calcium-/Phosphate-Induced Transdifferentiation and Calcification of Vascular Smooth Muscle Cells and Interferes with Matrix Metalloproteinase-2 and Metalloproteinase-9 and NF-kB

Abstract

Vascular calcifications bear the risk for cardiovascular complications and have a high prevalence among patients with chronic kidney disease. Central mediators of vascular calcifications are vascular smooth muscle cells (VSMC). They transdifferentiate into a synthetic/osteoblast-like phenotype, which is induced, for example, by elevated levels of calcium and phosphate (Ca/P) due to a disturbed mineral balance. An aqueous extract from Lindera obtusiloba (LOE) is known to exert antifibrotic and antitumor effects or to interfere with the differentiation of preadipocytes. Using murine and rat VSMC cell lines, we here investigated whether LOE also protects VSMC from Ca/P-induced calcification. Indeed, LOE effectively blocked Ca/P-induced calcification of VSMC as shown by decreased VSMC mineralization and secretion of alkaline phosphatase. In parallel, mRNA expression of the calcification markers osterix and osteocalcin was reduced. Vice versa, the Ca/P-induced loss of the VSMC differentiation markers alpha smooth muscle actin and smooth muscle protein 22-alpha was rescued by LOE. Further, LOE blocked Ca/P-induced mRNA expressions and secretions of matrix metalloproteinases-2/-9 and activation of NF-B, which are known contributors to vascular calcification. In conclusion, LOE interferes with the Ca/P-induced transdifferentiation/calcification of VSMC. Thus, LOE should be further analysed regarding a potential complementary treatment option for cardiovascular diseases including vascular calcifications.