Clearance of matrix metalloproteinase-9 is dependent on low-density lipoprotein receptor-related protein-1 expression downregulated by microRNA-205 in human abdominal aortic aneurysm

Journal of Vascular Surgery
Crystal Yin Tung ChanStephen Wing Keung Cheng

Abstract

Low-density lipoprotein receptor-related protein-1 (LRP1) has been suggested to be a crucial regulator in the pathogenesis of abdominal aortic aneurysm (AAA) from previous genome association and animal studies. Our prior study using human aortic samples has further revealed a significant reduction of LRP1 protein expression associated with AAA. However, the downregulation of LRP1 in the pathophysiology of AAA remained unresolved. We hypothesized that LRP1 downregulation may be mediated by microRNA (miR) and that LRP1 may function as a scavenger of matrix metalloproteinase-9 (MMP-9), a well-known protease for degradation of extracellular matrix proteins at the aortic wall for AAA pathogenesis. This study investigated the cause of LRP1 downregulation and its potential effect on AAA pathogenesis. An observational study of LRP1 protein, LRP1 messenger RNA (mRNA), and its three predicted miR candidates (miR-205, miR-338-5p, and miR-545-3p) was first performed in AAA compared with nonaneurysmal tissues from humans, followed by a functional study testing the effect on LRP1 expression of miR-205 overexpression and knockdown in human vascular smooth muscle cells (VSMCs) explant cultured from human abdominal aortic tissues. Lastly, anoth...Continue Reading

Citations

Mar 30, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Heng-Wei HsuMasashi Kitazawa
Mar 7, 2018·Oncotarget·Camille Boulagnon-RombiStéphane Dedieu
May 14, 2019·Frontiers in Cardiovascular Medicine·Nicola PotereStefano Toldo
Jul 8, 2020·International Journal of Molecular Sciences·Giovanni Barillari
Dec 12, 2020·Archives of Biochemistry and Biophysics·Yanan GuoXi-Long Zheng
Jul 11, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zhaohui HeMao Luo
Aug 5, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Yu-Xiao LiuBo Hu
Oct 27, 2021·European Journal of Clinical Investigation·Karlijn B RomboutsKak Khee Yeung

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