Share：
Share this content in WeChat
X
[Chinese][PDF]1572
• Original Article •
Experimental study on expression of TGF-β1 in fibrotic myocardium of rat by magnatic resonance targeted imaging
SONG Mengxing  XIA Min  YANG Yawen  MA Zhanlong 

Cite this article as: SONG M X, XIA M, YANG Y W, et al. Experimental study on expression of TGF-β1 in fibrotic myocardium of rat by magnatic resonance targeted imaging[J]. Chin J Magn Reson Imaging, 2024, 15(4): 120-125, 132. DOI:10.12015/issn.1674-8034.2024.04.019.


[Abstract] Objective To explore the feasibility of targeted magnetic resonance imaging (MRI) to detect transforming growth factor beta-1 (TGF-β1) expression by constructing superparamagnetic iron oxide (USPIO) nanoparticles that carry transforming growth factor-β1 antibody (TGF-β1).Materials and Methods Forty male SD rats were selected, of which 30 were modeled by isoprenaline subcutaneous injection, while the other 10 were used as healthy controls. Myocardial fibrosis modeling was evaluated by ultrasound. The 30 successfully modeled rats were randomly divided into the experimental group, simple control group, and blank control group. A TGF-β1 targeting probe (USPIO-anti-TGF-β1) was constructed and injected into experimental rats through the tail vein. The simple control and blank control groups were injected with the same dose of simple USPIO and normal saline. T2* weighted imaging was performed after 12 hours of injection to observe the change in myocardial signal intensity in the three groups. After MRI was completed, rat myocardium was taken as a specimen for pathological analysis. Independent-samples t test was used to analyze the changes of MRI signals before and after injection.Results Stable USPIO-anti-TGF-β1 probes were successfully prepared. MRI showed that the myocardial signal of rats in the experimental group remained uniform before administration. No significant low signal areas were observed. After 12 hours of administration, the subendocardial myocardium could be seen in the area of signal reduction. There was a significant difference in the relative signal strength of the two groups (0.72±0.12 vs. 0.62±0.10, P<0.01); There was no significant decrease in myocardial signal between the simple control group and the blank control group before and after administration (0.73±0.12 vs. 0.71±0.12, P＝0.81; 0.70±0.13 vs. 0.74±0.13, P=0.52). Masson staining showed that the area of myocardial fibrosis in the experimental group was consistent with the area of signal reduction shown by the MRI after administration. Immunohistochemistry showed positive expression of TGF-β1 in the myocardial fibrosis region. Prussian blue staining showed the deposition of iron particles in cardiomyocytes, which confirmed the presence of the USPIO-anti-TGF-β1 probe.Conclusions USPIO-anti-TGF-β1 probe can target magnetic resonance imaging of myocardial fibrosis, providing unprecedented ideas for the early diagnosis of myocardial fibrosis, providing experimental basis for monitoring of TGF-β1 expression and the selection and evaluation of anti fibrosis therapies.
[Keywords] transforming growth factor beta-1；ultrasmall supperparamagnetic iron oxide；targeting probe model of myocardial fibrosis in rat；magnetic resonance imaging

SONG Mengxing   XIA Min   YANG Yawen   MA Zhanlong*  

Department of Radiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China

Corresponding author: MA Z L, E-mail: mazhanlong@126.com

Conflicts of interest   None.

Received  2023-11-30
Accepted  2024-03-22
DOI: 10.12015/issn.1674-8034.2024.04.019
Cite this article as: SONG M X, XIA M, YANG Y W, et al. Experimental study on expression of TGF-β1 in fibrotic myocardium of rat by magnatic resonance targeted imaging[J]. Chin J Magn Reson Imaging, 2024, 15(4): 120-125, 132. DOI:10.12015/issn.1674-8034.2024.04.019.

[1]
ZEGARD A, OKAFOR O, DE BONO J, et al. Myocardial fibrosis as a predictor of sudden death in patients with coronary artery disease[J]. J Am Coll Cardiol, 2021, 77(1): 29-41. DOI: 10.1016/j.jacc.2020.10.046.
[2]
GIORDANO C, FRANCONE M, CUNDARI G, et al. Myocardial fibrosis: morphologic patterns and role of imaging in diagnosis and prognostication[J/OL]. Cardiovasc Pathol, 2022, 56: 107391 [2023-11-29]. https://pubmed.ncbi.nlm.nih.gov/34601072/. DOI: 10.1016/j.carpath.2021.107391.
[3]
ZHU L Y, WANG Y N, ZHAO S H, et al. Detection of myocardial fibrosis: where we stand[J/OL]. Front Cardiovasc Med, 2022, 9: 926378 [2023-11-29]. https://pubmed.ncbi.nlm.nih.gov/36247487/. DOI: 10.3389/fcvm.2022.926378.
[4]
BENGEL F M, DIEKMANN J, HESS A, et al. Myocardial fibrosis: emerging target for cardiac molecular imaging and opportunity for image-guided therapy[J/OL]. J Nucl Med, 2023, 64(Supplement 2): 49S-58S [2023-11-29]. https://pubmed.ncbi.nlm.nih.gov/37918842/. DOI: 10.2967/jnumed.122.264867.
[5]
XIA R, ZHU T, ZHANG Y, et al. Microcirculation of intramyocardial hemorrhage caused by reperfused myocardial infarctions with ultrasmall superparamagnetic iron oxide cardiac magnetic resonance imaging[J]. Acta Radiol, 2022, 63(11): 1469-1474. DOI: 10.1177/02841851211046332.
[6]
COLBERT C M, MING Z Y, POGOSYAN A, et al. Comparison of three ultrasmall, superparamagnetic iron oxide nanoparticles for MRI at 3.0 T[J]. J Magn Reson Imaging, 2023, 57(6): 1819-1829. DOI: 10.1002/jmri.28457.
[7]
BELKAHLA H, ANTUNES J C, LALATONNE Y, et al. USPIO-PEG nanoparticles functionalized with a highly specific collagen-binding peptide: a step towards MRI diagnosis of fibrosis[J]. J Mater Chem B, 2020, 8(25): 5515-5528. DOI: 10.1039/D0TB00887G.
[8]
THAYSE K, KINDT N, LAURENT S, et al. VCAM-1 target in non-invasive imaging for the detection of atherosclerotic plaques[J/OL]. Biology, 2020, 9(11): 368 [2023-11-29]. https://pubmed.ncbi.nlm.nih.gov/33138124/. DOI: 10.3390/biology9110368.
[9]
HANNA A, FRANGOGIANNIS N G. The role of the TGF-β superfamily in myocardial infarction[J/OL]. Front Cardiovasc Med, 2019, 6: 140 [2023-11-29]. https://pubmed.ncbi.nlm.nih.gov/31620450/. DOI: 10.3389/fcvm.2019.00140.
[10]
HUMERES C, VENUGOPAL H, FRANGOGIANNIS N G. Smad-dependent pathways in the infarcted and failing heart[J/OL]. Curr Opin Pharmacol, 2022, 64: 102207 [2023-11-29]. https://pubmed.ncbi.nlm.nih.gov/35367786/. DOI: 10.1016/j.coph.2022.102207.
[11]
FRANGOGIANNIS N G. Cardiac fibrosis: cell biological mechanisms, molecular pathways and therapeutic opportunities[J/OL]. Mol Aspects Med, 2019, 65: 70-99 [2023-11-29]. https://pubmed.ncbi.nlm.nih.gov/30056242/. DOI: 10.1016/j.mam.2018.07.001.
[12]
O'MEARA E, ZANNAD F. Fibrosis biomarkers predict cardiac reverse remodeling[J]. JACC Heart Fail, 2023, 11(1): 73-75. DOI: 10.1016/j.jchf.2022.11.011.
[13]
SCHLITTLER M, PRAMSTALLER P P, ROSSINI A, et al. Myocardial fibrosis in hypertrophic cardiomyopathy: a perspective from fibroblasts[J/OL]. Int J Mol Sci, 2023, 24(19): 14845 [2023-11-29]. https://pubmed.ncbi.nlm.nih.gov/37834293/. DOI: 10.3390/ijms241914845.
[14]
ONG C H, THAM C L, HARITH H H, et al. TGF-β-induced fibrosis: a review on the underlying mechanism and potential therapeutic strategies[J/OL]. Eur J Pharmacol, 2021, 911: 174510 [2023-11-29]. https://pubmed.ncbi.nlm.nih.gov/34560077/. DOI: 10.1016/j.ejphar.2021.174510.
[15]
FRANGOGIANNIS N G. Cardiac fibrosis[J]. Cardiovasc Res, 2021, 117(6): 1450-1488. DOI: 10.1093/cvr/cvaa324.
[16]
MA Y X, KUANG Y X, BO W Y, et al. Exercise training alleviates cardiac fibrosis through increasing fibroblast growth factor 21 and regulating TGF-β1-Smad2/3-MMP2/9 signaling in mice with myocardial infarction[J/OL]. Int J Mol Sci, 2021, 22(22): 12341 [2023-11-29]. https://pubmed.ncbi.nlm.nih.gov/34830222/. DOI: 10.3390/ijms222212341.
[17]
GE Z W, CHEN Y M, WANG B, et al. MFGE8 attenuates Ang-Ⅱ-induced atrial fibrosis and vulnerability to atrial fibrillation through inhibition of TGF-β1/Smad2/3 pathway[J/OL]. J Mol Cell Cardiol, 2020, 139: 164-175 [2023-11-29]. https://pubmed.ncbi.nlm.nih.gov/31958465/. DOI: 10.1016/j.yjmcc.2020.01.001.
[18]
SYGITOWICZ G, MACIEJAK-JASTRZĘBSKA A, SITKIEWICZ D. A review of the molecular mechanisms underlying cardiac fibrosis and atrial fibrillation[J/OL]. J Clin Med, 2021, 10(19): 4430 [2023-11-29]. https://pubmed.ncbi.nlm.nih.gov/34640448/. DOI: 10.3390/jcm10194430.
[19]
SONG M X, LU W Y, WU F, et al. Correlation of tenascin-X, tenascin-C and TGF-βexpression with formation of myocardial fibrosis in rats[J]. Chin J Geriatr Heart Brain Vessel Dis, 2022, 24(9): 975-978. DOI: 10.3969/j.issn.1009-0126.2022.09.020.
[20]
CHEN X L, WAN W G, RAN Q, et al. Pinocembrin mediates antiarrhythmic effects in rats with isoproterenol-induced cardiac remodeling[J/OL]. Eur J Pharmacol, 2022, 920: 174799 [2023-11-29]. https://pubmed.ncbi.nlm.nih.gov/35183531/. DOI: 10.1016/j.ejphar.2022.174799.
[21]
YOUSEFI F, SOLTANI B M, RABBANI S. MicroRNA-331 inhibits isoproterenol-induced expression of profibrotic genes in cardiac myofibroblasts via the TGFβ/smad3 signaling pathway[J/OL]. Sci Rep, 2021, 11(1): 2548 [2023-11-29]. https://pubmed.ncbi.nlm.nih.gov/33510328/. DOI: 10.1038/s41598-021-82226-z.
[22]
LU Y, HUANG J, NEVEROVA N V, et al. USPIOs as targeted contrast agents in cardiovascular magnetic resonance imaging[J]. Curr Cardiovasc Imaging Rep, 2021, 14(2): 2. DOI: 10.1007/s12410-021-09552-8.
[23]
DADFAR S M, CAMOZZI D, DARGUZYTE M, et al. Size-isolation of superparamagnetic iron oxide nanoparticles improves MRI, MPI and hyperthermia performance[J/OL]. J Nanobiotechnology, 2020, 18(1): 22 [2023-11-29]. https://pubmed.ncbi.nlm.nih.gov/31992302/. DOI: 10.1186/s12951-020-0580-1.
[24]
CHEN C, GE J X, GAO Y, et al. Ultrasmall superparamagnetic iron oxide nanoparticles: a next generation contrast agent for magnetic resonance imaging[J/OL]. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2022, 14(1): e1740 [2023-11-29]. https://pubmed.ncbi.nlm.nih.gov/34296533/. DOI: 10.1002/wnan.1740.
[25]
LAGAN J, NAISH J H, SIMPSON K, et al. Substrate for the myocardial inflammation-heart failure hypothesis identified using novel USPIO methodology[J]. JACC Cardiovasc Imaging, 2021, 14(2): 365-376. DOI: 10.1016/j.jcmg.2020.02.001.
[26]
KASSEM K M, ALI M, RHALEB N E. Interleukin 4: its role in hypertension, atherosclerosis, valvular, and nonvalvular cardiovascular diseases[J]. J Cardiovasc Pharmacol Ther, 2020, 25(1): 7-14. DOI: 10.1177/1074248419868699.
[27]
WANG Y, LI C F, ZHAO R Z, et al. CircUbe3a from M2 macrophage-derived small extracellular vesicles mediates myocardial fibrosis after acute myocardial infarction[J]. Theranostics, 2021, 11(13): 6315-6333. DOI: 10.7150/thno.52843.
[28]
RAO M, WANG X L, GUO G R, et al. Resolving the intertwining of inflammation and fibrosis in human heart failure at single-cell level[J/OL]. Basic Res Cardiol, 2021, 116(1): 55 [2023-11-29]. https://pubmed.ncbi.nlm.nih.gov/34601654/. DOI: 10.1007/s00395-021-00897-1.
[29]
TSAMPASIAN V, SWIFT A J, ASSADI H, et al. Myocardial inflammation and energetics by cardiac MRI: a review of emerging techniques[J/OL]. BMC Med Imaging, 2021, 21(1): 164 [2023-11-29]. https://pubmed.ncbi.nlm.nih.gov/34749671/. DOI: 10.1186/s12880-021-00695-0.
[30]
MERINOPOULOS I, GUNAWARDENA T, STIRRAT C, et al. Diagnostic applications of ultrasmall superparamagnetic particles of iron oxide for imaging myocardial and vascular inflammation[J]. JACC Cardiovasc Imaging, 2021, 14(6): 1249-1264. DOI: 10.1016/j.jcmg.2020.06.038.
[31]
XIA M, WU F, YANG Y, et al. The possibility of visualizing TGF-β1 expression in ApoE-/- mice atherosclerosis using MR targeted imaging[J]. Acta Radiol, 2024, 65(1): 99-105. DOI: 10.1177/02841851231153989.
[32]
LU W Y, SONG M X, WU F, et al. Experimental study on expression of tenascin-X in fibrotic myocardium of rat by magnetic resonance targeted imaging[J]. Adv Cardiovasc Dis, 2022, 43(5): 463-468. DOI: 10.16806/j.cnki.issn.1004-3934.2022.05.019.
[33]
SHIRAKAWA K, ENDO J, KATAOKA M, et al. MerTK expression and ERK activation are essential for the functional maturation of osteopontin-producing reparative macrophages after myocardial infarction[J/OL]. J Am Heart Assoc, 2020, 9(18): e017071 [2023-11-29]. https://pubmed.ncbi.nlm.nih.gov/32865099/. DOI: 10.1161/JAHA.120.017071.
[34]
CAI S S, ZHAO M Y, ZHOU B, et al. Mitochondrial dysfunction in macrophages promotes inflammation and suppresses repair after myocardial infarction[J/OL]. J Clin Investig, 2023, 133(4) [2023-11-29]. https://www.jci.org/articles/view/159498. DOI: 10.1172/jci159498.
[35]
YANG P B, CHEN Z W, HUANG W, et al. Communications between macrophages and cardiomyocytes[J/OL]. Cell Commun Signal, 2023, 21(1): 206 [2023-11-29]. https://pubmed.ncbi.nlm.nih.gov/37587464/. DOI: 10.1186/s12964-023-01202-4.

PREV Relationship between CSF inflow into the cerebral glymphatic system of AD mice and age: A visualization study based on 9.4 T DCE-MRI
NEXT 7.0 T magnetic resonance imaging evaluation of left ventricular function improvement in rats with pulmonary arterial hypertension in the Qinghai-Tibet Plateau environment following sodium selenite administration: A preliminary study
  


LINK


Tel & Fax: +8610-67113815    E-mail: editor@cjmri.cn