title: The CD147/MMP-2 signaling pathway may regulate early stage cardiac remodelling in spontaneously hypertensive rats.
abstract: Previous studies have reported that decreased matrix metalloproteinase-2 (MMP-2) is associated with early stage (age 8-16 weeks) ventricular remodelling in spontaneously hypertensive rats (SHR). We hypothesized that inhibited CD147/MMP-2 signalling might down-regulate MMP-2 expression and augment remodelling in spontaneously hypertensive rats. Twenty-nine male SHR (8 weeks) were randomly assigned to SHR, CD147, and CD147+DOX groups. The control group included eight age-matched WKY rats. CD147 and CD147+DOX groups received recombinant human CD147 (600 ng/kg in 1.5 mL saline, weekly). The SHR and WKY groups received the vehicle. The CD147+DOX group also received doxycycline, an inhibitor of MMPs (daily, 30 mg/kg in 1.5 mL saline, iG). On day 56 echocardiography and left ventricular mass index (LVWI) measurements were collected and histological sections were stained for cell and collagen content. Myocardium MMP-2, TIMP-1, CD147, and collagens types I and III were estimated by western blot. CD147 and the ratio of MMP-2/TIMP-1 were lower in SHR than WKY rats (P<.05). Myocyte hypertrophy, partial fibre breaks, plasmolysis, necrosis and collagen content (collagen volume fraction [CVF], I and III) in SHR were above control levels (P<.05). CD147 rats showed CD147, MMP-2 and MMP-2/TIMP-1 were increased (P<.05), CVF, LVWI, and collagen I and III were decreased (P<.05) and myocyte morphology was improved. CD147 levels did not differ between CD147+DOX and CD147 groups, CVF, collagens type I and III and partial fiber breaks were more abundant in CD147+DOX (P<.05). In summary, an inhibited CD147/MMP-2 pathway was associated with early stage cardiac remodelling, and CD147 supplementation may attenuate this response.
authors.affiliation: Department of Internal Cardiology, The First Affiliated Hospital of Guang Dong Pharmaceutical University (School of Clinical Medicine), Guangzhou, China.
authors.forename: Bowei
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Internal Cardiology, The First Affiliated Hospital of Guang Dong Pharmaceutical University (School of Clinical Medicine), Guangzhou, China. zhouwanx2015@sina.com.
authors.forename: Wanxing
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of Guang Dong Pharmaceutical University (School of Clinical Medicine), Guangzhou, China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Internal Cardiology, The First Affiliated Hospital of Guang Dong Pharmaceutical University (School of Clinical Medicine), Guangzhou, China.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Internal Cardiology, The First Affiliated Hospital of Guang Dong Pharmaceutical University (School of Clinical Medicine), Guangzhou, China.
authors.forename: Yongjing
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Internal Cardiology, The First Affiliated Hospital of Guang Dong Pharmaceutical University (School of Clinical Medicine), Guangzhou, China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Guang Dong Pharmaceutical University (School of Clinical Medicine), Guangzhou, China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Song
authors.affiliation: The School of Life Science of Guang Dong Pharmaceutical University, Guangzhou, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Internal Cardiology, The First Affiliated Hospital of Guang Dong Pharmaceutical University (School of Clinical Medicine), Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D051926:Basigin / Q000378:metabolism* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology*
chemical_list: C497886:BSG protein, human; D051926:Basigin; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat
keywords: CD147; matrix metalloproteinase-2; spontaneously hypertensive rats; ventricular remodelling