Dataset Information

Loureirin B Alleviates Myocardial Ischemia/Reperfusion Injury via Inhibiting PAI-1/TGF-β1/Smad Signaling Pathway.

ABSTRACT: Myocardial ischemia/reperfusion (MI/R) injury is a common clinical problem after myocardial infarction without effective therapy. Loureirin B (LrB) is a kind of flavonoid with anti-inflammatory and antifibrotic activities. However, the effect of LrB on MI/R and its underlying mechanism remains elusive. In the present study, a mouse model of MI/R was established by coronary artery occlusion. Administration of LrB (0.5 mg/kg or 1 mg/kg) for 4 weeks effectively improved left ventricular (LV) function and reduced myocardial infarction in MI/R mice. MI/R-induced expression of IL-6, TNF-α, and IL-1β in the hearts was reduced by LrB treatment. Histological analysis showed that LrB attenuated myocardial collagen deposition. LrB downregulated fibronectin, collagen I, collagen III, and α-SMA expression. Notably, LrB inhibited the expression of profibrotic plasminogen activator inhibitor-1 (PAI-1), transforming growth factor (TGF)-β1, TGF-β1R, and p-Smad2/3. Consistently, LrB inhibited the activation of TGF-β1/Smad signaling pathway and the expression of fibrosis-related proteins in angiotensin (Ang) II-treated cardiac fibroblasts (CFs). Overexpression of PAI-1 abolished the effects of LrB on Ang II-treated CFs, suggesting that LrB may function through regulating PAI-1. These results indicated that LrB may alleviate MI/R-induced myocardial fibrosis by inhibiting PAI-1/TGF-β1/Smad signaling pathway. Thus, LrB may be a potential drug in the treatment of MI/R injury.

SUBMITTER: Kong F

PROVIDER: S-EPMC9078770 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Loureirin B Alleviates Myocardial Ischemia/Reperfusion Injury via Inhibiting PAI-1/TGF-<i>β</i>1/Smad Signaling Pathway.

Kong Fei F Zhao Meng M

Evidence-based complementary and alternative medicine : eCAM 20220430

Myocardial ischemia/reperfusion (MI/R) injury is a common clinical problem after myocardial infarction without effective therapy. Loureirin B (LrB) is a kind of flavonoid with anti-inflammatory and antifibrotic activities. However, the effect of LrB on MI/R and its underlying mechanism remains elusive. In the present study, a mouse model of MI/R was established by coronary artery occlusion. Administration of LrB (0.5 mg/kg or 1 mg/kg) for 4 weeks effectively improved left ventricular (LV) functi ...[more]

PMID: 35535157

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Project description:Background/aimsThe activation of the complement system and subsequent inflammatory responses are important features of myocardial ischemia/reperfusion (I/R) injury. Exosomes are nanoscale extracellular vesicles that play a significant role in remote ischemic preconditioning (RIPC) cardioprotection. The present study aimed to test whether RIPC-induced plasma exosomes (RIPC-Exo) exert protective effects on myocardial I/R injury by inhibiting complement activation and inflammation and whether exosomal heat shock protein 90 (HSP90) mediates these effects.MethodsRat hearts underwent 30 min of coronary ligation followed by 2 h of reperfusion. Plasma exosomes were isolated from RIPC rats and injected into the infarcted myocardium immediately after ligation. Sixty rats were randomly divided into Sham, I/R, I/R + RIPC-Exo (50 µg/µl), and RIPC-Exo + GA (geldanamycin, 1 mg/kg, administration 30 min before ligation) groups. Cardiomyocyte apoptosis, the release of myocardial markers (LDH, cTnI and CK-MB), infarct size, the expression of HSP90, complement component (C)3, C5a, c-Jun N-terminal kinase (JNK), interleukin (IL)-1β, tumor necrosis factor (TNF)-alpha and intercellular adhesion molecule -1 (ICAM-1) were assessed.ResultsRIPC-Exo treatment significantly reduced I/R-induced cardiomyocyte apoptosis, the release of myocardial markers (LDH, cTnI and CK-MB) and infarct size. These beneficial effects were accompanied by decreased C3 and C5a expression, decreased inflammatory factor levels (IL-1β, TNF-α, and ICAM-1), decreased JNK and Bax, and increased Bcl-2 expression. Meanwhile, the expression of HSP90 in the exosomes from rat plasma increased significantly after RIPC. However, treatment with HSP90 inhibitor GA significantly reversed the cardioprotection of RIPC-Exo, as well as activated complement component, JNK signalling and inflammation, indicating that HSP90 in exosomes isolated from the RIPC was important in mediating the cardioprotective effects during I/R.ConclusionExosomal HSP90 induced by RIPC played a significant role in cardioprotection against I/R injury, and its function was in part linked to the inhibition of the complement system, JNK signalling and local and systemic inflammation, ultimately alleviating I/R-induced myocardial injury and apoptosis by the upregulation of Bcl-2 expression and the downregulation of proapoptotic Bax.

Dataset Information

Loureirin B Alleviates Myocardial Ischemia/Reperfusion Injury via Inhibiting PAI-1/TGF-β1/Smad Signaling Pathway.

Publications

Loureirin B Alleviates Myocardial Ischemia/Reperfusion Injury via Inhibiting PAI-1/TGF-<i>β</i>1/Smad Signaling Pathway.

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