scholarly journals miR-155 down-regulation protects the heart from hypoxic damage by activating fructose metabolism in cardiac fibroblasts

2021 ◽  
Author(s):  
Yu Zhang ◽  
Hong Zhang ◽  
Zhan Yang ◽  
Xin-hua Zhang ◽  
Qing Miao ◽  
...  
Keyword(s):  
Cardiac Fibroblasts ◽  
Down Regulation ◽  
Fructose Metabolism

Abstract 58: AT2 Receptor Agonism Regulates TIMP1/MMP9 Axis in the Heart Preventing Cardiac Fibrosis and Improving Heart Function After Experimental Myocardial Infarction

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Dilyara Lauer ◽  
Svetlana Slavic ◽  
Manuela Sommerfeld ◽  
Christa Thöne-Reineke ◽  
Yuliya Sharkovska ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Left Ventricle ◽  
Late Stage ◽  
Heart Function ◽  
Cardiac Fibroblasts ◽  
Collagen Content ◽  
Vehicle Group ◽  
At2 Receptor ◽  
Down Regulation ◽  
Tgf Β1

Aims: A selective nonpeptide agonist for the angiotensin AT2 receptor compound 21 (C21) improved cardiac functions 7 days after myocardial infarction (MI). Here, we aimed to investigate what are the cellular mechanisms underlying cardiac protection in the late stage after MI. Methods and Results: MI was induced in Wistar rats by permanent ligation of the left coronary artery. Treatment with C21 (0.03mg/kg i.p. daily) started 6h after MI and continued for 6 weeks. Hemodynamic parameters were measured via transthoracic Doppler echocardiography and intracardiac Samba catheter. The expression of MMP9, TIMP1, TGF-β1 and collagen content were determined in left ventricle. Anti-proteolytic effects were additionally studied in primary cardiac fibroblasts. C21 significantly improved systolic and diastolic function 6 weeks after MI in comparison with the vehicle group as shown by ejection fraction (71.2±4.7 % vs. 53.4±7.0%; p<0.001), fractional shortening (40.8±2.3% vs. 30.9±3.1%; p<0.05), LVIDs (4.4±0.5mm vs. 5.2±0.8mm; p<0.05), LV EDP (16.9±1.2mmHg vs. 22.1±1.4mmHg; p<0.05), E/A ratio, dP/dt max and dP/dt min (p<0.05). Moreover, C21 improved arterial stiffness parameter (AIx) (18±1.2% vs. 25%±1.8, p<0.05) and reduced collagen content (15%; p<0.05) in postinfarcted myocardium. TIMP1 protein expression in the left ventricle was strongly up-regulated (17.7-fold; p<0.05) whereas MMP9 and TGF-β1 were significantly down-regulated (1.5-fold, p<0.05; 3.4-fold p<0.001, respectively) in the treated group. In cardiac fibroblasts, C21 primarily induced TIMP1 expression followed by attenuated MMP9 secretion and TGF-β1 down-regulation. Conclusion: C21 improves heart function in the late stage after MI and prevents cardiac remodeling. Activation of TIMP1 and subsequent inhibition of MMP9-mediated proteolysis as well as down-regulation of TGF-β1 followed by decreased collagen accumulation may attenuate disintegration of the extracellular matrix and reduce fibrosis.

scholarly journals MicroRNA-9 inhibits high glucose-induced proliferation, differentiation and collagen accumulation of cardiac fibroblasts by down-regulation of TGFBR2

2016 ◽  
Vol 36 (6) ◽  
Author(s):  
Jiaxin Li ◽  
Yingnan Dai ◽  
Zhendong Su ◽  
Guoqian Wei
Keyword(s):  
Protective Effect ◽  
High Glucose ◽  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Down Regulation ◽  
Qrt Pcr ◽  
Collagen Accumulation

To investigate the effects of miR-9 on high glucose (HG)-induced cardiac fibrosis in human cardiac fibroblasts (HCFs), and to establish the mechanism underlying these effects. HCFs were transfected with miR-9 inhibitor or mimic, and then treated with normal or HG. Cell viability and proliferation were detected by using the Cell Counting Kit-8 (CCK-8) assay and Brdu-ELISA assay. Cell differentiation and collagen accumulation of HCFs were detected by qRT-PCR and Western blot assays respectively. The mRNA and protein expressions of transforming growth factor-β receptor type II (TGFBR2) were determined by qRT-PCR and Western blotting. Up-regulation of miR-9 dramatically improved HG-induced increases in cell proliferation, differentiation and collagen accumulation of HCFs. Moreover, bioinformatics analysis predicted that the TGFBR2 was a potential target gene of miR-9. Luciferase reporter assay demonstrated that miR-9 could directly target TGFBR2. Inhibition of TGFBR2 had the similar effect as miR-9 overexpression. Down-regulation of TGFBR2 in HCFs transfected with miR-9 inhibitor partially reversed the protective effect of miR-9 overexpression on HG-induced cardiac fibrosis in HCFs. Up-regulation of miR-9 ameliorates HG-induced proliferation, differentiation and collagen accumulation of HCFs by down-regulation of TGFBR2. These results provide further evidence for protective effect of miR-9 overexpression on HG-induced cardiac fibrosis.

scholarly journals Infarct-Induced Steroidogenic Acute Regulatory Protein: A Survival Role in Cardiac Fibroblasts

2013 ◽  
Vol 27 (9) ◽  
pp. 1502-1517 ◽  
Author(s):  
Eli Anuka ◽  
Natalie Yivgi-Ohana ◽  
Sarah Eimerl ◽  
Benjamin Garfinkel ◽  
Naomi Melamed-Book ◽  
...  
Keyword(s):  
Hela Cells ◽  
Cardiac Fibroblasts ◽  
Primary Cultures ◽  
Regulatory Protein ◽  
Steroidogenic Acute Regulatory Protein ◽  
Mouse Heart ◽  
Heart Cells ◽  
Down Regulation ◽  
Apparent Lack ◽  
Steroidogenic Acute Regulatory

Steroidogenic acute regulatory protein (StAR) is indispensable for steroid hormone synthesis in the adrenal cortex and the gonadal tissues. This study reveals that StAR is also expressed at high levels in nonsteroidogenic cardiac fibroblasts confined to the left ventricle of mouse heart examined 3 days after permanent ligation of the left anterior descending coronary artery. Unlike StAR, CYP11A1 and 3β-hydroxysteroid dehydrogenase proteins were not observed in the postinfarction heart, suggesting an apparent lack of de novo cardiac steroidogenesis. Work with primary cultures of rat heart cells revealed that StAR is induced in fibroblasts responding to proapoptotic treatments with hydrogen peroxide or the kinase inhibitor staurosporine (STS). Such induction of StAR in culture was noted before spontaneous differentiation of the fibroblasts to myofibroblasts. STS induction of StAR in the cardiac fibroblasts conferred a marked resistance to apoptotic cell death. Consistent with that finding, down-regulation of StAR by RNA interference proportionally increased the number of STS-treated apoptotic cells. StAR down-regulation also resulted in a marked increase of BAX activation in the mitochondria, an event known to associate with the onset of apoptosis. Last, STS treatment of HeLa cells showed that apoptotic demise characterized by mitochondrial fission, cytochrome c release, and nuclear fragmentation is arrested in individual HeLa cells overexpressing StAR. Collectively, our in vivo and ex vivo evidence suggests that postinfarction expression of nonsteroidogenic StAR in cardiac fibroblasts has novel antiapoptotic activity, allowing myofibroblast precursor cells to survive the traumatized event, probably to differentiate and function in tissue repair at the infarction site.

Disruption of histamine H2 receptor slows heart failure progression through reducing myocardial apoptosis and fibrosis

2014 ◽  
Vol 127 (7) ◽  
pp. 435-448 ◽  
Author(s):  
Zhi Zeng ◽  
Liang Shen ◽  
Xixian Li ◽  
Tao Luo ◽  
Xuan Wei ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Down Regulation ◽  
Histamine H2 Receptor ◽  
H2 Receptor ◽  
Mitochondrial Permeability ◽  
Myocardial Apoptosis ◽  
Heart Failure Progression

In the present study, we have shown that H2R deficiency or blockade could reduce cardiac fibrosis through the down-regulation of calcineurin expression in cardiac fibroblasts and reduce myocardial apoptosis through lowering of mitochondrial permeability in cardiomyocytes, finally achieving the goal of improving heart failure.

Protective role of peroxiredoxin-4 in heart failure

2020 ◽  
Vol 134 (1) ◽  
pp. 71-72
Author(s):  
Naseer Ahmed ◽  
Masooma Naseem ◽  
Javeria Farooq
Keyword(s):  
Heart Failure ◽  
Cardiac Fibroblasts ◽  
Protective Role ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Total Antioxidant ◽  
Galectin 3 ◽  
Consequent Increase ◽  
And Oxidative Stress

Abstract Recently, we have read with great interest the article published by Ibarrola et al. (Clin. Sci. (Lond.) (2018) 132, 1471–1485), which used proteomics and immunodetection methods to show that Galectin-3 (Gal-3) down-regulated the antioxidant peroxiredoxin-4 (Prx-4) in cardiac fibroblasts. Authors concluded that ‘antioxidant activity of Prx-4 had been identified as a protein down-regulated by Gal-3. Moreover, Gal-3 induced a decrease in total antioxidant capacity which resulted in a consequent increase in peroxide levels and oxidative stress markers in cardiac fibroblasts.’ We would like to point out some results stated in the article that need further investigation and more detailed discussion to clarify certain factors involved in the protective role of Prx-4 in heart failure.

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