2. Academic Validation
  3. The miR-378c-Samd1 circuit promotes phenotypic modulation of vascular smooth muscle cells and foam cells formation in atherosclerosis lesions

The miR-378c-Samd1 circuit promotes phenotypic modulation of vascular smooth muscle cells and foam cells formation in atherosclerosis lesions

  • Sci Rep. 2021 May 18;11(1):10548. doi: 10.1038/s41598-021-89981-z.
Shengya Tian # 1,  Yang Cao # 2,  Jinliang Wang # 3,  Yongjun Bi 4,  Jingquan Zhong 5,  Xiangbin Meng 6,  Wenyu Sun 7,  Ruixue Yang 5,  Luping Gan 8,  Xuping Wang 5,  Hongshi Li 5,  Rong Wang 9 10
Affiliations

Affiliations

  • 1 Division of Hematology and Oncology, Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School (HMS), Boston, MA, 02215, USA.
  • 2 Department of Medicine/Division of Cardiology, University of California, Los Angeles, CA, USA.
  • 3 Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA.
  • 4 Clinical Laboratory, Central Hospital of Xinwen Mining Group, 164 Xinkuang Road, Xintai, 271233, Shandong, China.
  • 5 The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, China.
  • 6 Department of Cardiac Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, China.
  • 7 Department of Cardiac Surgery, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, 266035, Shandong, China.
  • 8 Department of Anesthesiology, The People's Hospital of Yichun Jiangxi, Yichun, 336000, Jiangxi, China.
  • 9 The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, China. [email protected].
  • 10 Department of Cardiology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA. [email protected].
  • # Contributed equally.
PMID: 34006929 DOI: 10.1038/s41598-021-89981-z
Abstract

MicroRNAs have emerged as key regulators in vascular diseases and are involved in the formation of atherosclerotic lesions. However, the atherosclerotic-specific MicroRNAs and their functional roles in atherosclerosis are unclear. Here, we report that miR-378c protects against atherosclerosis by directly targeting Sterile Alpha Motif Domain Containing 1 (Samd1), a predicted transcriptional repressor. miR-378c was strikingly reduced in atherosclerotic plaques and blood of acute coronary syndrome (ACS) patients relative to healthy controls. Suppression of miR-378c promoted vascular smooth muscle cells (VSMCs) phenotypic transition during atherosclerosis. We also reported for the first time that Samd1 prolonged immobilization of LDL on the VSMCs, thus facilitated LDL oxidation and subsequently foam cell formation. Further, we found that Samd1 contains predicted DNA binding domain and directly binds to DNA regions as a transcriptional repressor. Together, we uncovered a novel mechanism whereby miR-378c-Samd1 circuit participates in two key elements of atherosclerosis, VSMCs phenotypic transition and LDL oxidation. Our results provided a better understanding of atherosclerosis pathophysiology and potential therapeutic management by targeting miR-378c-Samd1 circuit.

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