Sp1 Plays an Important Role in Vascular Calcification Both In Vivo and In Vitro

Abstract

BackgroundVascular calcification and increased cardiovascular morbidity and mortality are closely related in patients with end‐stage renal disease and diabetes mellitus. Specific protein 1 (Sp1) is a transactivation molecule that plays a crucial role in the regulation of apoptosis, fibrosis, angiogenesis, and other pathological disorders. There is evidence that specific protein 1 (Sp1) directly stimulates the transcription of bone morphogenetic protein 2 (BMP2) and that BMP2 plays a key role in the calcification process in the BMP2–expressing F9 cell model system. Here, we investigated whether Sp1 plays an important role in vascular calcification and its potential regulatory mechanism in vascular calcification.Methods and ResultsIn this study, vascular calcification was induced in male Wistar rats by administration of nicotine (25 mg/kg) and vitamin D3 (300 000 IU/kg). These rats were randomly selected for treatment with adenovirus harboring Sp1 knockdown gene or empty virus. The mechanism of Sp1 in vascular smooth muscle cells cultured in high phosphate medium was studied. Based on our findings, the Sp1 gene silencing or inhibition improved calcium deposition, which was partly achieved by inhibiting phenotype switch, apoptosis, and matrix vesicle release of vascular smooth muscle cells. Moreover, Sp1 can activate BMP2 transcription by binding to the Sp1‐binding element of the BMP2 promoter.ConclusionsOverall, elevated Sp1 exerts a pro‐apoptotic effect, promoting BMP2 transcription and further accumulating vascular calcification. Proper and timely regulation of Sp1 expression may be a potential strategy for treatment of aging, end‐stage renal disease, and diabetic‐related macrovascular disease treatment.

Prostaglandin E1 Inhibited Diabetes-Induced Phenotypic Switching of Vascular Smooth Muscle Cells Through Activating Autophagy

“…Diabetes-induced vascular complication was associated with phenotypic modulation of VSMCs, switching from a contractile to a synthetic-proliferative phenotype [1]. In the preliminary study, we confirmed that 25mM glucose could induce the phenotypic switching of VSMCs and showed no significant effects in cell viability.…”

“…VSMCs undergo phenotype switching in T2DM patients or diabetic rats, which might be associated with the onset or progression of atherogenic process [1]. However, the underlying molecular mechanisms mediating phenotypic change of VSMCs remain not entirely understood.…”

Acute Effects of the Consumption of Passiflora setacea Juice on Metabolic Risk Factors and Gene Expression Profile in Humans

“…Studies on the effect of bioactive compounds (BC) on this transcription factor showed that orientin, isoorientin, vitexin, and isovitexin exert suppressive action of these compounds upon NF-κB activation [24]. Elevated SP1 plays a pro-apoptotic effect and stimulates vascular calcification [83]. It has been observed that the BC (-)-epigallocatechin-3-gallate can modulate the activity of this transcription factor [84].…”

Extracellular Vesicle microRNAs Contribute to the Osteogenic Inhibition of Mesenchymal Stem Cells in Multiple Myeloma

“…Specificity Protein 1 (Sp1) is a key transcription factor involved in several biological pathways, acting as positive or negative gene expression regulator; in particular it plays a critical role in cell proliferation, cell cycle progression and apoptosis [29][30][31]. Emerging studies report a role of Sp1 in OB differentiation; in fact, its downregulation prevents vascular calcification by inhibiting the transdifferentiation of vascular smooth muscle cells into OBs [32]. In addition, Sp1 increases the mineralization of osteoblastic cells [33].…”