Geraniol enhances peroxiredoxin-1, and prevents isoproterenol-induced oxidative stress and inflammation associated with myocardial infarction in experimental animal models.

This study has explored the fact that geraniol prevents isoproterenol (ISO)-induced oxidative stress and inflammation-mediated myocardial infarction (MI) through enhanced expression of peroxiredoxin-1 (Prdx-1) in experimental animal models. The experimental strategies of MI were stimulated through the subcutaneous direction of ISO (85 mg/kg body weight) for 14 days. ISO-directed models showed elevated heart rate levels and cardiac markers (serum creatine kinase [CK], serum CK-myocardial band, serum C-reactive proteins, and plasma homocysteine); increased cardiac-troponins-T, and troponin-I levels in both serum and myocardium. Moreover, we perceived that a higher level of lipid peroxidation molecules (thiobarbituric acid reactive substances and lipid hydroperoxides) reduced the antioxidant enzyme levels in plasma and heart tissue of ISO-directed rats. However, geraniol treatment prevents ISO-directed enhancement of the heart rate, cardiac and lipid peroxidative genes; reverted the blood pressure, and antioxidant status in ISO-directed rats. Furthermore, gene expression results revealed that geraniol treatment inhibited the mitogen-activated protein kinase (MAPK) proteins, inflammatory responder (tumor necrosis factor-α, interleukin 6, nuclear factor-κB), and cardiac fibrotic proteins (matrix metalloproteinase-2[MMP-2], MMP-9) in ISO directed rats. Prdx-1 is an antioxidant response element, and it can regulate all the antioxidant proteins and it scavenges harmful radicals. Therefore, enhanced Prdx-1 expression is considered to have a pivotal role in preventing cardiac infarction. In this study, an elevated expression of Prdx1 was noticed in geraniol treated with ISO-directed rats. Hence, we concluded that geraniol is considered a potential phytodrug, and it prevents ISO-directed MAPKs, inflammation, and cardiac markers by enhancing the expression of Prdx1.

Knockdown of lncRNA PVT1 Inhibits Vascular Smooth Muscle Cell Apoptosis and Extracellular Matrix Disruption in a Murine Abdominal Aortic Aneurysm Model.

This study was designed to determine the effects of the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) on vascular smooth muscle cell (VSMC) apoptosis and extracellular matrix (ECM) disruption in a murine abdominal aortic aneurysm (AAA) model. After injection of PVT1-silencing lentiviruses, AAA was induced in Apolipoprotein E-deficient (ApoE-/-) male mice by angiotensin II (Ang II) infusion for four weeks. After Ang II infusion, mouse serum levels of pro-inflammatory cytokines were analysed, and aortic tissues were isolated for histological, RNA, and protein analysis. Our results also showed that PVT1 expression was significantly upregulated in abdominal aortic tissues from AAA patients compared with that in controls. Additionally, Ang II treatment significantly increased PVT1 expression, both in cultured mouse VSMCs and in AAA murine abdominal aortic tissues. Of note, the effects of Ang II in facilitating cell apoptosis, increasing matrix metalloproteinase (MMP)-2 and MMP-9, reducing tissue inhibitor of MMP (TIMP)-1, and promoting switching from the contractile to synthetic phenotype in cultured VSMCs were enhanced by overexpression of PVT1 but attenuated by knockdown of PVT1. Furthermore, knockdown of PVT1 reversed Ang II-induced AAA-associated alterations in mice, as evidenced by attenuation of aortic diameter dilation, marked adventitial thickening, loss of elastin in the aorta, enhanced aortic cell apoptosis, elevated MMP-2 and MMP-9, reduced TIMP-1, and increased pro-inflammatory cytokines. In conclusion, our findings demonstrate that knockdown of lncRNA PVT1 suppresses VSMC apoptosis, ECM disruption, and serum pro-inflammatory cytokines in a murine Ang II-induced AAA model.

Inhibition of miR-155 attenuates abdominal aortic aneurysm in mice by regulating macrophage-mediated inflammation.

The aim of the present study was to identify abdominal aortic aneurysms (AAA)-associated miR-155 contributing to AAA pathology by regulating macrophage-mediated inflammation. Angiotensin II (AngII)-infused apolipoprotein E-deficient (ApoE-/-) mice and THP-1 cells model of miR-155 overexpression and deficiency were used in the experiments. The expression of miR-155 was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cytokines were evaluated using enzyme-linked immunoabsorbent assay (ELISA). Western blotting was used to measure the levels of MMP-2, MMP-9, iNOS, and monocyte chemoattractant protein (MCP)-1 proteins. Immunostaining and transwell were used to determine CD68, elastic collagen, proliferation, and migration of vascular smooth muscle cells (VSMCs). The results showed that miR-155 and cytokines were up-regulated in AAA patients or ApoE-/- mice. Overexpression of miR-155 enhanced MMP-2, MMP-9, iNOS, and MCP-1 levels, and stimulated the proliferation and migration of VSMCs. Meanwhile, inhibition of miR-155 had the opposite effect. In addition, histology demonstrated accumulation of CD68 and elastic collagen-positive areas significantly decreased in miR-155 antagomir injection group. In conclusion, the results of the present study suggest that inhibiting miR-155 is crucial to prevent the development of AAA by regulating macrophage inflammation.