The influence of rosuvastatin therapy and percutaneous coronary intervention on angiogenic growth factors in coronary artery disease patients

Семенова, А. Е.; Sergienko, I. A.; Масенко, В П; Ezhov, M.; Габрусенко, С. А.; Kuharchuk, V. V.; Belenkov, Yuriy

doi:10.2143/ac.64.3.2038029

Cited by 15 publications

(7 citation statements)

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“…Several authors have shown that IL-6 overexpression could lead to a commercial application for therapeutic angiogenesis, because of enhanced neovascularization in ischemic diseases. 29,30 IL-6 may induce angiogenesis in blood vascular ECs via increased TGF-β1-mediated endogenous production of angiogenic growth factors. The observed increase in angiogenesis of blood vascular ECs may in turn promote the proliferation of FBs.…”

Section: Il-6 Promotes Myocardial Fibrosis J-h Wang Et Almentioning

confidence: 99%

Hypoxia-stimulated cardiac fibroblast production of IL-6 promotes myocardial fibrosis via the TGF-β1 signaling pathway

Wang

Zhao

Pan

et al. 2016

Laboratory Investigation

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Interlukin-6 (IL-6) is a multifunctional cytokine produced by several cell types that has a role in fibrosis. Fibroblasts (FBs) maintain this underlying pathogenic change through regulation of IL-6 production; however, its potential functional role in regulating surrounding cellular structural changes during ischemic myocardial remodeling remains unexplored. Here, we generated FBs, cardiomyocytes (CMs), and blood vascular endothelial cells (ECs) from the ventricles of neonatal rats. IL-6 was then overexpressed in FBs and the cells were treated with IL-6 receptor inhibitor (IL6RI), TGF-β1 receptor inhibitor (TβRI), or MMP2/MMP9 inhibitor (MMPI) using monoculture or coculture models under hypoxic conditions. The results indicate that overexpression of IL-6 is sufficient to induce myofibroblastic proliferation, differentiation, and fibrosis, probably via increased TGF-β1-mediated MMP2/MMP3 signaling. The use of IL6RI, TβRI, or MMPI diminished these effects. In addition, IL-6 activated the apoptosis-associated factors Caspase3 and Smad3, and decreased the expression of anti-apoptotic factor Bcl2, resulting in apoptosis of CMs under hypoxic coculture: IL6RI or TβRI inhibited these effects. Unexpectedly, IL-6-overexpressing FBs significantly increased the angiogenesis of ECs, which involved significant increases in the expression of proangiogenic growth factors. Treatment of FBs with IL6RI or TβRI in coculture with ECs reduced the levels of secreted proangiogenic growth factors, and the angiogenesis of ECs was significantly downregulated. Thus, IL-6 functions in ischemic myocardial remodeling through multifunctional reprogramming of hypoxia-associated FBs towards fibrosis via upregulation of the TGF-β1 signaling pathway.

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Section: Il-6 Promotes Myocardial Fibrosis J-h Wang Et Almentioning

confidence: 99%

Hypoxia-stimulated cardiac fibroblast production of IL-6 promotes myocardial fibrosis via the TGF-β1 signaling pathway

Wang

Zhao

Pan

et al. 2016

Laboratory Investigation

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“…Statins are HMG-CoA reductase inhibitors that can reduce the synthesis and secretion of intracellular cholesterol, facilitate serum cholesterol removal, and inhibit the synthesis of apolipoprotein [ 29 ]. The effect of statins has been recognized in the prevention of coronary heart disease [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Rosuvastatin and MiR-126 on Myocardial Injury Induced by Acute Myocardial Infarction in Rats: Role of Vascular Endothelial Growth Factor A (VEGF-A)

et al. 2016

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BackgroundThe present study investigated the effects of VEGF-A targeted by miR-126 on myocardial injury after acute myocardial infarction (AMI) in rats, along with the contributions of rosuvastatin to the synergic effect.Material/MethodsSD rats were obtained to construct AMI models by ligating their left anterior descending coronary arteries (LAD). We conducted echocardiography to check the 6 involved indexes: left ventricular ejection fractions (LVEF), fractional shortening (FS), left ventricular end-systolic volume (LVV), left ventricular end-diastolic volume (LVVd), cardiac output (CO), and heart rate (HR). Moreover, antibody sandwich enzyme-linked immunosorbent assay was carried out to determine MI markers: creatine kinase (CK), CK Isoenzyme (CK-MB), and Troponin I (cTn I). Dual-Luciferase Reporter Assay was performed to confirm the targeting of miR-126 and VEGF-A. MTT assay provided insight into the proliferation of myocardial fibroblasts. Finally, RT-RCR and Western blot were used for the detection of miR-126 and VEGF-A expressions in vivo and in vitro.ResultsLuciferase activity assay showed that miR-126 transfection significantly decreased the relative luciferase activity in HEK293T cells when it was bound to normal 3′ UTR of VEGF-A (P<0.05). In comparison to the control group, rats in the AMI model group had significantly lower LVEF, FS, and CO, and substantially higher LVVs, LVVd, HR, CK/U, CK-MB/U, and cTn-1/U (all P<0.05). Down-regulated miR-126 and up-regulated VEGF-A were also observed in MI models (P<0.05).ConclusionsmiR-126 and rosuvastatin have protective effects on AMI risk, and VEGF-A antagonizes effects on AMI is imposed by.

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“…Interestingly there are studies proving that statin treatment can reduce VEGF levels in serum as well as atherosclerotic plaque volume [107,108]. In a study using statins and more specifically fluvastatin, in a mouse model demonstrated that statin treatment can have beneficial effects by inhibiting the up-regulation of angiogenic molecules such as VEF, HIF-1α and phospho-STAT3.…”

Section: Statins For Treating Pathological Angiogenesismentioning

confidence: 99%

Anti-Angiogenic Therapy and Cardiovascular Diseases: Current Strategies and Future Perspectives

Katsi

Psarros²,

Krokidis³

et al. 2014

Anti-Angiogenesis Drug Discovery and Development

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The influence of rosuvastatin therapy and percutaneous coronary intervention on angiogenic growth factors in coronary artery disease patients

Cited by 15 publications

References 0 publications

Hypoxia-stimulated cardiac fibroblast production of IL-6 promotes myocardial fibrosis via the TGF-β1 signaling pathway

Hypoxia-stimulated cardiac fibroblast production of IL-6 promotes myocardial fibrosis via the TGF-β1 signaling pathway

Effects of Rosuvastatin and MiR-126 on Myocardial Injury Induced by Acute Myocardial Infarction in Rats: Role of Vascular Endothelial Growth Factor A (VEGF-A)

Anti-Angiogenic Therapy and Cardiovascular Diseases: Current Strategies and Future Perspectives

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