Augmentation of phosphate-induced osteo-/chondrogenic transformation of vascular smooth muscle cells by homoarginine

Abstract

Homoarginine augments osteo-/chondrogenic transformation of VSMCs and vascular calcification, effects involving impaired NO formation from homoarginine.

SGK1 induces vascular smooth muscle cell calcification through NF-κB signaling

“…The origin of these mice was described previously (22). Subtotal nephrectomy was performed during isoflurane anesthesia (1.5%-2%) as previously described (6). In a first step, the right kidney mass was reduced by electrocauterization and surgical excision.…”

“…MAoSMCs were grown to confluence in DMEM/F12 medium (Thermo Fisher Scientific) supplemented with 10% FBS (Thermo Fisher Scientific), 100 U/ ml penicillin, 100 μg/ml streptomycin (Thermo Fisher Scientific), and 0.025 μg/ml Fungizone (Thermo Fisher Scientific). The cells were used in all experiments from passages [3][4][5][6]. N indicates the number of independent experiments from 3 independent isolations of MAoSMCs.…”

“…Sgk1-deficient and corresponding WT mice were injected s.c. with 400,000 IU/kg body weight of cholecalciferol (Sigma-Aldrich) or vehicle for 3 days as previously described (6,44). For EMD638683 experiments, C57BL/6 mice received twice-daily oral gavage with 300 mg/kg body weight EMD638683 (Biorbyt); control mice received only vehicle.…”

“…[RUNX2]) (6) and msh homeobox 2 (MSX2) (7). Furthermore, the transformed VSMCs express tissue-nonspecific ALPL (alkaline phosphatase, liver/bone/kidney), which cleaves the powerful calcification inhibitor pyrophosphate (PPi) (8).…”

Oxidative Stress, Inflammation, and Vascular Aging in Hypertension

“…34 These processes promote VSMC transformation with vascular calcification and have been linked to impaired NO formation and homoarginine. 35 NO can inhibit NADPH oxidases. 36 Gao et al demonstrated a potentially important practical application of this observation to explain the mechanism by which dietary nitrate reduces BP.…”