PMID- 29572322 OWN - NLM STAT- MEDLINE DCOM- 20191209 LR - 20231213 IS - 2047-9980 (Electronic) IS - 2047-9980 (Linking) VI - 7 IP - 6 DP - 2018 Mar 23 TI - Sp1 Plays an Important Role in Vascular Calcification Both In Vivo and In Vitro. LID - 10.1161/JAHA.117.007555 [doi] LID - e007555 AB - BACKGROUND: Vascular 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 RESULTS: In 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. CONCLUSIONS: Overall, 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. CI - (c) 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. FAU - Zhang, Xinyu AU - Zhang X AD - Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, the State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, China. FAU - Li, Rui AU - Li R AD - Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, the State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, China. FAU - Qin, Xiaoteng AU - Qin X AD - Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, the State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, China. FAU - Wang, Lei AU - Wang L AD - Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, the State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, China. FAU - Xiao, Jie AU - Xiao J AD - Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, the State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, China. FAU - Song, Yu AU - Song Y AD - Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, the State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, China. FAU - Sheng, Xi AU - Sheng X AD - Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, the State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, China. FAU - Guo, Mengqi AU - Guo M AD - Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, the State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, China. FAU - Ji, Xiaoping AU - Ji X AD - Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, the State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, China Jixiaoping@sdu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180323 PL - England TA - J Am Heart Assoc JT - Journal of the American Heart Association JID - 101580524 RN - 0 (Bmp2 protein, rat) RN - 0 (Bone Morphogenetic Protein 2) RN - 0 (Sp1 Transcription Factor) RN - 0 (SP1 protein, human) RN - 1C6V77QF41 (Cholecalciferol) RN - 6M3C89ZY6R (Nicotine) SB - IM MH - Animals MH - Apoptosis MH - Binding Sites MH - Bone Morphogenetic Protein 2/genetics/metabolism MH - *Cell Transdifferentiation MH - Cholecalciferol MH - Disease Models, Animal MH - Humans MH - Male MH - Muscle, Smooth, Vascular/*metabolism/pathology MH - Myocytes, Smooth Muscle/*metabolism/pathology MH - Nicotine MH - Osteoblasts/*metabolism/pathology MH - Phenotype MH - Promoter Regions, Genetic MH - Rats, Wistar MH - Signal Transduction MH - Sp1 Transcription Factor/genetics/*metabolism MH - Transcriptional Activation MH - Vascular Calcification/chemically induced/genetics/*metabolism/pathology PMC - PMC5907546 OTO - NOTNLM OT - BMP2 OT - Sp1 OT - apoptosis OT - calcification OT - phenotype switching of vascular smooth muscle cells EDAT- 2018/03/25 06:00 MHDA- 2019/12/18 06:00 PMCR- 2018/03/20 CRDT- 2018/03/25 06:00 PHST- 2018/03/25 06:00 [entrez] PHST- 2018/03/25 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2018/03/20 00:00 [pmc-release] AID - JAHA.117.007555 [pii] AID - JAH33060 [pii] AID - 10.1161/JAHA.117.007555 [doi] PST - epublish SO - J Am Heart Assoc. 2018 Mar 23;7(6):e007555. doi: 10.1161/JAHA.117.007555.