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A Model of Cardiac Remodeling Through Constriction of the Abdominal Aorta in Rats
Published on: December 2, 2016
The CD147/MMP-2 signaling pathway may regulate early stage cardiac remodelling in spontaneously hypertensive rats
Bowei Li1, Wanxing Zhou2, Xiaorong Yang3
1Department of Internal Cardiology, The First Affiliated Hospital of Guang Dong Pharmaceutical University (School of Clinical Medicine), Guangzhou, China.
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.
Insights
Inhibited CD147/matrix metalloproteinase-2 (MMP-2) signaling worsens cardiac remodeling in hypertensive rats. CD147 supplementation may protect against this early-stage ventricular remodeling.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Hypertension Research
Background:
- Decreased matrix metalloproteinase-2 (MMP-2) is linked to early ventricular remodeling in spontaneously hypertensive rats (SHR).
- The CD147/MMP-2 signaling pathway's role in this process requires further investigation.
Purpose of the Study:
- To investigate the hypothesis that inhibited CD147/MMP-2 signaling exacerbates cardiac remodeling in SHR.
- To evaluate the therapeutic potential of CD147 supplementation in attenuating cardiac remodeling.
Main Methods:
- Twenty-nine male SHR were assigned to SHR, CD147, or CD147+doxycycline (DOX) groups; eight WKY rats served as controls.
- Echocardiography, left ventricular mass index (LVWI), and histological analyses were performed.
- Myocardial expression of CD147, MMP-2, TIMP-1, and collagen types I and III were quantified via Western blot.
Main Results:
- SHR exhibited lower CD147 and MMP-2/TIMP-1 ratios, alongside increased myocyte hypertrophy, collagen content (CVF, types I & III), and LVWI compared to WKY rats.
- CD147 supplementation in SHR increased CD147 and MMP-2/TIMP-1, while decreasing CVF, LVWI, and collagen types I & III, improving myocyte morphology.
- Co-administration with doxycycline (MMP inhibitor) negated the protective effects of CD147 supplementation, with increased CVF, collagen types I & III, and fiber breaks.
Conclusions:
- An inhibited CD147/MMP-2 pathway is associated with early-stage cardiac remodeling in SHR.
- CD147 supplementation demonstrates potential to attenuate cardiac remodeling by modulating the MMP-2 pathway.
- Targeting the CD147/MMP-2 axis may offer a novel therapeutic strategy for hypertensive cardiac remodeling.
