Extracellular vesicles derived from myocardial infarction plasma inhibit BMSCs apoptosis and enhance cardiac function via AKT signaling pathway

2021 ◽  
Vol 96 ◽  
pp. 107730
Author(s):  
Peifeng Jin ◽  
Lu Ding ◽  
Lei Wang ◽  
Sheng Jiang ◽  
Jiakan Weng ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Signaling Pathway ◽  
Extracellular Vesicles ◽  
Akt Signaling ◽  
Akt Signaling Pathway

scholarly journals 6-Gingerol Protects Heart by Suppressing Myocardial Ischemia/Reperfusion Induced Inflammation via the PI3K/Akt-Dependent Mechanism in Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Tongtong Xu ◽  
Guowei Qin ◽  
Wei Jiang ◽  
Ying Zhao ◽  
Yongnan Xu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Myocardial Ischemia ◽  
Inflammatory Response ◽  
Cardiac Function ◽  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Myocardial Ischemia Reperfusion

Our previous study has demonstrated that 6-Gingerol (6-G) could alleviate myocardial ischemia/reperfusion injury (MIRI). However, the molecular mechanism underlying the process of myocardial ischemia/reperfusion (I/R) injury alleviation by 6-G remains unelucidated. The objective of the present study is to further investigate the potential mechanism for 6-G to alleviate MIRI in rats. Thirty-two Sprague-Dawley rats were randomly divided into four groups: the Sham group, the I/R group, the 6-G + I/R group, and the LY294002 (LY) + 6-G + I/R group. For the rats in each of the groups, data were collected for cardiogram, cardiac function, area of myocardial infarction, myocardial pathology, myocardial enzyme, marker of inflammatory response, and PI3K/Akt signaling pathway. We found that the pretreatment of 6-G with 6 mg/kg could shrink the ST section of cardiogram, improve the cardiac function, reduce the area of myocardial infarction and the degree of cardiac pathological injury, lower the level of myocardial enzyme, and inhibit the inflammatory response. In addition, our results also indicated that 6-G could upregulate the expression of PI3K and p-Akt and that LY294002, a blocking agent of PI3K/Akt signaling pathway, could nullify the protecting role of 6-G. Our experimental results showed that 6-G could inhibit I/R-induced inflammatory response through the activation of the PI3K/Akt signaling pathway.

scholarly journals PO-163 Aerobic exercise activates myocardial FGF21/FGFR1/PI3K-AKT signaling pathway and inhibits cardiomyocyte apoptosis in post-myocardial infarction rats

2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Mingxiao Li ◽  
Zhenjun Tian
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Aerobic Exercise ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Collagen Fibers ◽  
Cardiomyocyte Apoptosis ◽  
Akt Pathway ◽  
Akt Signaling Pathway ◽  
Myocardial Apoptosis

Objective To investigate the effect of aerobic exercise on the expression of fibroblast growth factor 21 (FGF21) and cardiomyocyte apoptosis in Myocardial Infarction (MI) rats. Methods male SD rats were randomly divided into three groups：the sham operation (S), sedentary MI group (MI) and MI with aerobic exercise group (ME). The MI model was established by ligation of the left anterior descending branch of the left coronary artery. ME group were trained four weeks after the operation. LVSP, LVEDP and ±dp/dtmax were used to evaluate cardiac function. H9C2 cardiomyocytes were stimulated by 400 μmol/L H2O2 for 4h to simulate myocardial apoptosis mode. AMPK agonist AICAR and FGF21 receptor inhibitor PD166866 were used to interfere with H9C2. Myocardial collagen volume fraction was calculated by Masson staining and myocardium FGF21, FGFR1, Bax, Bcl-2 and PI3K-AKT pathway by western blotting or RT-Qpcr. Cardiomyocytes apoptosis was evaluated by TUNEL. Results Compared with S, the expression of FGF21, FGFR1, Bax, Bcl-2 and PI3K, AKT increased significantly in MI group, the apoptotic cardiomyocytes and collagen fibers increased significantly, but the cardiac function decreased. Compared to MI, myocardium FGF21, FGFR1 and PI3K, AKT were further increased in ME group, the Bax/Bcl-2 and the apoptotic cardiomyocytes decreased significantly. The percentage of collagen fibers decreased and the cardiac function was improved. Myocardium FGF21 was positively correlated with the inhibition of cardiomyocyte apoptosis and the improvement of cardiac function. Furthermore, the expression of Bax/Bcl-2, TNF-α/IL-10 and the apoptotic cardiomyocytes was significantly increased by PD166866, but PI3K-AKT pathway decreased significantly by PD166866. However, AICAR single intervention or PD166866 simultaneous intervention also can reverse this adverse effects. Conclusions Exercise can increase myocardial FGF21/FGFR1 with MI. The one of the mechanisms is to activate PI3K-AKT pathway to inhibit cardiaomyocyte apoptosis and inflammatory. It indicates that FGF21/FGFR1/PI3K-AKT signaling pathway plays an important role in inhibiting myocardial apoptosis and improving cardiac function.

scholarly journals Thyroid hormone mediates cardioprotection against postinfarction remodeling and dysfunction through the IGF-1/PI3K/AKT signaling pathway

2020 ◽  
Author(s):  
Bin Zeng ◽  
Xiaoting Liao ◽  
Lei Liu ◽  
Caixia Zhang ◽  
Huaiyu Ruan
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Diseases ◽  
Thyroid Hormone ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Left Ventricular ◽  
Sham Operation ◽  
Akt Signaling Pathway ◽  
Anti Inflammatory ◽  
Related Proteins

Abstract Background Severe cardiovascular diseases, such as myocardial infarction or heart failure, can alter thyroid hormone (TH) secretion and peripheral conversion, leading to low triiodothyronine (T3) syndrome. Accumulating evidence suggests that TH has protective properties against cardiovascular diseases and that treatment with TH can effectively reduce myocardial damage after myocardial infarction (MI). However, the potential mechanisms are not clear. This study was designed to investigate the effect of T3 pretreatment on cardiac function and pathological changes in mice subjected to MI and the underlying mechanisms. Methods Adult male C57BL/6 mice underwent surgical ligation of the left anterior descending coronary artery (LAD) (or sham operation) to establish a myocardial infarction model. T3, BMS-754807 (inhibitor of insulin-like growth factor-1 receptor (IGF-1R)) or vehicle was administered before surgery. Results Compared with the MI group, the T3 pretreatment group exhibited significant attenuation of the myocardial infarct area, inhibition of cardiomyocyte apoptosis and fibrosis, and improved left ventricular function after MI. In addition, T3 exhibited an enhanced potency to stimulate angiogenesis and exert anti-inflammatory effects by reducing the levels of serum inflammatory cytokines after myocardial infarction. However, all of these protective effects were inhibited by the IGF-1R inhibitor BMS-754807. Moreover, the protein expression of IGF-1/PI3K/AKT signaling-related proteins, such as IGF-1, IGF-1R, phosphorylated PI3K (p-PI3K) and p-AKT was significantly upregulated in MI mice that received T3 pretreatment, and BMS-754807 pretreatment blocked the upregulation of the expression of these signaling-related proteins. Conclusion T3 pretreatment can protect the heart against dysfunction post-MI through its anti-apoptotic, anti-fibrotic, anti-inflammatory and angiogenesis-stimulating effects, which may be mediated by the activation of the IGF-1/PI3K/AKT signaling pathway.

scholarly journals Osteosarcoma Cell-Derived Small Extracellular Vesicles Enhance Osteoclastogenesis and Bone Resorption Through Transferring MicroRNA-19a-3p

2021 ◽  
Vol 11 ◽  
Author(s):  
Tingting Luo ◽  
Xiaocheng Zhou ◽  
Erhui Jiang ◽  
Lin Wang ◽  
Yaoting Ji ◽  
...  
Keyword(s):  
Bone Metastasis ◽  
Signaling Pathway ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Osteoclast Differentiation ◽  
Bone Destruction ◽  
Akt Signaling ◽  
Osteosarcoma Cell ◽  
Akt Signaling Pathway ◽  
Micro Computed Tomography

Osteosarcoma (OS) is the most common primary bone cancer characterized by an aggressive phenotype with bone destruction. The prognosis of OS patients remains unoptimistic with the current treatment strategy. Recently, osteoclasts are believed to play a crucial role in cancer bone metastasis. Thus, osteoclast could be a target both in bone destruction and cancer progression in OS. However, mechanisms governing osteoclastogenesis in OS remain poorly understood. miRNA delivered by small extracellular vesicles (sEVs) could mediate cellular communications. In this study, we investigated the effects of sEVs on osteoclastogenesis and osteoclast function, also clarified the underlying mechanism. We herein found that sEVs promoted pre-osteoclast migration, osteoclastogenesis and resorption by exposing RAW264.7 cells to sEVs derived from OS cells. Bioinformatics analysis showed that phosphatase tension homologue (PTEN), and miR-19a-3p were involved in OS progression. Overexpression of miR-19a-3p or sEVs’ miR-19a-3p promoted osteoclast formation and function through PTEN/PI3K/AKT signaling pathway, while inhibition of miR-19a-3p showed the contrary results. The bone marrow macrophages (BMMs) were used to verify the results. OS mice, which were established by subcutaneous injection of OS cells, exhibited increased levels of sEVs’ miR-19a-3p in blood. Moreover, micro-computed tomography (CT) and histomorphometry analysis demonstrated that OS mice exhibited osteopenia with increased number of osteoclasts. In conclusion, miR-19a-3p delivery via OS cell-derived sEVs promotes osteoclast differentiation and bone destruction through PTEN/phosphatidylinositol 3 -kinase (PI3K)/protein kinase B (AKT) signaling pathway. These findings highlight sEVs packaging of miR-19a-3p as a potential target for prevention and treatment of bone destruction and cancer progression in OS patients. And this finding provides a novel potentially therapeutic target for the bone metastasis.

Sign in / Sign up

Export Citation Format

Share Document