Glucocorticoid ameliorates early cardiac dysfunction after coronary microembolization and suppresses TGF-β1/Smad3 and CTGF expression.
OBJECTIVE
This study was designed to evidence the protective effect of glucocorticoid therapy on cardiac dysfunction after coronary microembolization (CME), and to clarify its mechanism with the expression of transforming growth factor-beta 1 (TGF-β1)/Smad3 and connective tissue growth factor (CTGF).


METHODS
Eighteen mini-pigs were studied, including Sham-operation group (n=4), CME group (n=8) and Glucocorticoid therapy group (n=6, received methylprednisolone 25mg/kg intravenously 30 min before CME). Magnetic resonance imaging (3.0-T) was performed at baseline, 6th hour and one week after operation to evaluate cardiac function. Serum TGF-β1, CTGF and troponin T were also detected. Myocardial expressions of TGF-β1, CTGF and Smad3 were detected by western blot and immunohistochemistry. Total collagen expression was demonstrated by Masson Trichrome stain.


RESULTS
Compared with Sham-operation group, left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV) in CME group were increased at 6th hour after CME, while left ventricular ejection fraction (LVEF) was decreased significantly. Compared with CME group, methylprednisolone greatly improved LVEF after CME (6th hour: 56.0 ± 3.2% vs. 51.8 ± 3.8%, P=0.030; one week: 57.8 ± 3.2% vs. 54.6 ± 2.6%, P=0.053). We found that methylprednisolone not only significantly decreased serum TGF-β1, CTGF and troponin T, but also reduced myocardial expressions of TGF-β1, CTGF and Smad3 after CME. In addition, collagen volume fraction in glucocorticoid therapy group was markedly lower than that in CME group.


CONCLUSIONS
Glucocorticoid therapy could improve early cardiac function after CME, and its mechanism could be associated with TGF-β1/Smad3 and CTGF suppression.
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China.
Zhangwei
Z
Chen
Juying
J
Qian
Jianying
J
Ma
Shufu
S
Chang
Hong
H
Yun
Hang
H
Jin
Aijun
A
Sun
Yunzeng
Y
Zou
Junbo
J
Ge
D000818:Animals; D015415:Biomarkers / Q000097:blood; D055513:Connective Tissue Growth Factor / Q000037:antagonists & inhibitors / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood / Q000628:therapy; D004621:Embolization, Therapeutic / Q000379:methods*; D005260:Female; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051900:Smad3 Protein / Q000037:antagonists & inhibitors / Q000097:blood*; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000097:blood*
D015415:Biomarkers; D005938:Glucocorticoids; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor