Alpha 2.0

» Articles » PMID: 31924749

Loss of PARP-1 Attenuates Diabetic Arteriosclerotic Calcification Via Stat1/Runx2 Axis

Overview

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2020 Jan 12

PMID 31924749

Citations 25

Authors

Authors

Peng Li

Ying Wang

Xue Liu

Bin Liu

Zhao-Yang Wang

Fei Xie

Wen Qiao

Er-Shun Liang

Qing-Hua Lu

Ming-Xiang Zhang

Affiliations

Affiliations

Soon will be listed here.

Abstract

Accelerated atherosclerotic calcification is responsible for plaque burden, especially in diabetes. The regulatory mechanism for atherosclerotic calcification in diabetes is poorly characterized. Here we show that deletion of PARP-1, a main enzyme in diverse metabolic complications, attenuates diabetic atherosclerotic calcification and decreases vessel stiffening in mice through Runx2 suppression. Specifically, PARP-1 deficiency reduces diabetic arteriosclerotic calcification by regulating Stat1-mediated synthetic phenotype switching of vascular smooth muscle cells and macrophage polarization. Meanwhile, both vascular smooth muscle cells and macrophages manifested osteogenic differentiation in osteogenic media, which was attenuated by PARP-1/Stat1 inhibition. Notably, Stat1 acts as a positive transcription factor by directly binding to the promoter of Runx2 and promoting atherosclerotic calcification in diabetes. Our results identify a new function of PARP-1, in which metabolism disturbance-related stimuli activate the Runx2 expression mediated by Stat1 transcription to facilitate diabetic arteriosclerotic calcification. PARP-1 inhibition may therefore represent a useful therapy for this challenging complication.

Citing Articles

Ectopic calcifications in the musculoskeletal field: the basis for preventive and curative pharmacological strategies.

Milovanovic P, Savic I, Popovic A, Grajic M Clin Rheumatol. 2025; 44(3):869-886.

PMID: 39853559 DOI: 10.1007/s10067-025-07335-w.

: A possible target for vascular calcification.

Pan X, Song Y, Liang Y, Feng G, Wang Z Heliyon. 2024; 10(21):e39865.

PMID: 39524709 PMC: 11550659. DOI: 10.1016/j.heliyon.2024.e39865.

Targeted NAD repletion via biomimetic nanoparticle enables simultaneous management of intimal hyperplasia and accelerated re-endothelialization: A proof-of-concept study toward next-generation of endothelium-protective, anti-restenotic therapy.

Yin L, Tong Y, Xie R, Zhang Z, Islam Z, Zhang K J Control Release. 2024; 376:806-815.

PMID: 39461367 PMC: 11611612. DOI: 10.1016/j.jconrel.2024.10.045.

CBL-b E3 ligase-mediated neddylation and activation of PARP-1 induce vascular calcification.

Kwon D, Shin S, Nam Y, Choe N, Lim Y, Jeong A Exp Mol Med. 2024; 56(10):2246-2259.

PMID: 39349831 PMC: 11541702. DOI: 10.1038/s12276-024-01322-y.

Regulated vascular smooth muscle cell death in vascular diseases.

Yin Z, Zhang J, Shen Z, Qin J, Wan J, Wang M Cell Prolif. 2024; 57(11):e13688.

PMID: 38873710 PMC: 11533065. DOI: 10.1111/cpr.13688.

References

1.

Gong L, Liu F, Wang Y, Hou X, Zhang W, Qin W . Poly (ADP-ribose) transferase/polymerase-1-deficient mice resistant to age-dependent decrease in β-cell proliferation. Mol Med. 2012; 18:816-24. PMC: 3409279. DOI: 10.2119/molmed.2011.00458. View

2.

Mori S, Takemoto M, Yokote K, Asaumi S, Saito Y . Hyperglycemia-induced alteration of vascular smooth muscle phenotype. J Diabetes Complications. 2002; 16(1):65-8. DOI: 10.1016/s1056-8727(01)00189-1. View

3.

Tintut Y, Patel J, Territo M, Saini T, Parhami F, Demer L . Monocyte/macrophage regulation of vascular calcification in vitro. Circulation. 2002; 105(5):650-5. DOI: 10.1161/hc0502.102969. View

4.

Ohmori Y, Hamilton T . IL-4-induced STAT6 suppresses IFN-gamma-stimulated STAT1-dependent transcription in mouse macrophages. J Immunol. 1998; 159(11):5474-82. View

5.

Beranger G, Momier D, Rochet N, Carle G, Scimeca J . Poly(adp-ribose) polymerase-1 regulates Tracp gene promoter activity during RANKL-induced osteoclastogenesis. J Bone Miner Res. 2007; 23(4):564-71. DOI: 10.1359/jbmr.071111. View

6.

Wei S, Cheng L, Liang E, Wang Q, Zhou S, Xu H . Poly(ADP-ribose) polymerase 1 deficiency increases nitric oxide production and attenuates aortic atherogenesis through downregulation of arginase II. Clin Exp Pharmacol Physiol. 2016; 44(1):114-122. DOI: 10.1111/1440-1681.12685. View

7.

Kassan M, Choi S, Galan M, Bishop A, Umezawa K, Trebak M . Enhanced NF-κB activity impairs vascular function through PARP-1-, SP-1-, and COX-2-dependent mechanisms in type 2 diabetes. Diabetes. 2013; 62(6):2078-87. PMC: 3661639. DOI: 10.2337/db12-1374. View

8.

Naik V, Leaf E, Hu J, Yang H, Nguyen N, Giachelli C . Sources of cells that contribute to atherosclerotic intimal calcification: an in vivo genetic fate mapping study. Cardiovasc Res. 2012; 94(3):545-54. PMC: 3353803. DOI: 10.1093/cvr/cvs126. View

9.

Sun Y, Byon C, Yuan K, Chen J, Mao X, Heath J . Smooth muscle cell-specific runx2 deficiency inhibits vascular calcification. Circ Res. 2012; 111(5):543-52. PMC: 3678289. DOI: 10.1161/CIRCRESAHA.112.267237. View

10.

Rouleau M, Patel A, Hendzel M, Kaufmann S, Poirier G . PARP inhibition: PARP1 and beyond. Nat Rev Cancer. 2010; 10(4):293-301. PMC: 2910902. DOI: 10.1038/nrc2812. View

11.

Deng L, Huang L, Sun Y, Heath J, Wu H, Chen Y . Inhibition of FOXO1/3 promotes vascular calcification. Arterioscler Thromb Vasc Biol. 2014; 35(1):175-83. PMC: 4270841. DOI: 10.1161/ATVBAHA.114.304786. View

12.

Steitz S, Speer M, Curinga G, Yang H, Haynes P, Aebersold R . Smooth muscle cell phenotypic transition associated with calcification: upregulation of Cbfa1 and downregulation of smooth muscle lineage markers. Circ Res. 2001; 89(12):1147-54. DOI: 10.1161/hh2401.101070. View

13.

Zhang X, Zhou M, Guo Y, Song Z, Liu B . 1,25-Dihydroxyvitamin D₃ Promotes High Glucose-Induced M1 Macrophage Switching to M2 via the VDR-PPARγ Signaling Pathway. Biomed Res Int. 2015; 2015:157834. PMC: 4417570. DOI: 10.1155/2015/157834. View

14.

Kishi Y, Fujihara H, Kawaguchi K, Yamada H, Nakayama R, Yamamoto N . PARP Inhibitor PJ34 Suppresses Osteogenic Differentiation in Mouse Mesenchymal Stem Cells by Modulating BMP-2 Signaling Pathway. Int J Mol Sci. 2015; 16(10):24820-38. PMC: 4632778. DOI: 10.3390/ijms161024820. View

15.

Ziros P, Rojas Gil A, Georgakopoulos T, Habeos I, Kletsas D, Basdra E . The bone-specific transcriptional regulator Cbfa1 is a target of mechanical signals in osteoblastic cells. J Biol Chem. 2002; 277(26):23934-41. DOI: 10.1074/jbc.M109881200. View

16.

Ndip A, Wilkinson F, Jude E, Boulton A, Alexander M . RANKL-OPG and RAGE modulation in vascular calcification and diabetes: novel targets for therapy. Diabetologia. 2014; 57(11):2251-60. DOI: 10.1007/s00125-014-3348-z. View

17.

Fu Y, Gao C, Liang Y, Wang M, Huang Y, Ma W . Shift of Macrophage Phenotype Due to Cartilage Oligomeric Matrix Protein Deficiency Drives Atherosclerotic Calcification. Circ Res. 2016; 119(2):261-76. DOI: 10.1161/CIRCRESAHA.115.308021. View

18.

Cai Z, Ding Y, Zhang M, Lu Q, Wu S, Zhu H . Ablation of Adenosine Monophosphate-Activated Protein Kinase α1 in Vascular Smooth Muscle Cells Promotes Diet-Induced Atherosclerotic Calcification In Vivo. Circ Res. 2016; 119(3):422-33. DOI: 10.1161/CIRCRESAHA.116.308301. View

19.

Ding Y, Zhang M, Zhang W, Lu Q, Cai Z, Song P . AMP-Activated Protein Kinase Alpha 2 Deletion Induces VSMC Phenotypic Switching and Reduces Features of Atherosclerotic Plaque Stability. Circ Res. 2016; 119(6):718-30. PMC: 6265658. DOI: 10.1161/CIRCRESAHA.116.308689. View

20.

Raaz U, Schellinger I, Chernogubova E, Warnecke C, Kayama Y, Penov K . Transcription Factor Runx2 Promotes Aortic Fibrosis and Stiffness in Type 2 Diabetes Mellitus. Circ Res. 2015; 117(6):513-24. PMC: 4553105. DOI: 10.1161/CIRCRESAHA.115.306341. View