Differential gene expression profiles in spontaneously hypertensive rats induced by administration of enalapril and nifedipine

Lee, Ki-Mo; Kang, Haeng-A; Ko, Chang-Bo; Oh, Eunha; Park, Min; Lee, Hwa-Youn; Choi, Hyungsub; Yun, Chul‐Ho; Jung, Woon‐Won; Oh, Jae-Wook; Kang, Hyung‐Sik

doi:10.3892/ijmm.2012.1183

Cited by 11 publications

(8 citation statements)

References 35 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It cannot be ruled out that in the experimental conditions, enalapril upregulates coordinately expression of both NF-kB and IGF-IR (shown in our studies) since IGF-IR promoter contains NF-kB binding site (Ma et al 2006 ). Such a hypothesis seems to be reasonable since recently it was found that enalapril and nifedipine differentially regulate 33 genes involved in the pathogenesis of cardiovascular diseases (Lee et al 2013 ).…”

Section: Discussionmentioning

confidence: 96%

Enalapril stimulates collagen biosynthesis through prolidase-dependent mechanism in cultured fibroblasts

Szoka

Karna

Morka

et al. 2015

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

The mechanism of a lower incidence of dermatological manifestations in patients treated with enalapril compared to patients treated with other ACE-inhibitors, e.g., captopril, is not known. The finding that prolidase plays an important role in collagen biosynthesis and that some angiotensin-converting enzyme inhibitors affect prolidase activity led us to evaluate its effect on collagen biosynthesis in cultured human skin fibroblasts. Since insulin-like growth factor (IGF-I) and transforming growth factor beta 1 (TGF-β1) are the most potent stimulators of both collagen biosynthesis and prolidase activity, and prolidase is regulated by β1 integrin signaling, the effect of enalapril and enalaprilat on IGF-IR, TGF-β1, and β1 integrin receptor expressions was evaluated. Cells were treated with milimolar concentrations (0.3 and 0.5 mM) of enalapril and enalaprilat for 24 h. The activity of prolidase was determined by colorimetic assay. Collagen biosynthesis was evaluated by radiometric assay. Expression of signaling proteins was evaluated using Western blot. It was found that enalapril- and enalaprilat-dependent increase in prolidase activity and expression was accompanied by parallel increase in collagen biosynthesis. The exposure of the cells to 0.5 mM enalapril and enalaprilat contributed to increase in IGF-IR and α2β1 integrin receptor as well as TGF-β1 and NF-κB p65 expressions. Enalapril- and enalaprilat-dependent increase of collagen biosynthesis in fibroblasts results from increase of prolidase activity and expression, which may undergo through activation of α2β1 integrin and IGF-IR signaling as well as upregulation of TGF-β1 and NF-κB p65, the inhibitor of collagen gene expression.

show abstract

Section: Discussionmentioning

confidence: 96%

Enalapril stimulates collagen biosynthesis through prolidase-dependent mechanism in cultured fibroblasts

Szoka

Karna

Morka

et al. 2015

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

show abstract

“…There are significant data showing that treatment with anti-hypertensive drugs leads to changes in gene expression in the kidneys and bladder tissue ( 4 , 5 ). Additionally, a recent study demonstrated that treatment with such drugs may also result in changes in gene expression directly in the heart, brain and liver tissues ( 6 ). The authors reported on differentially expressed genes following treatment with anti-hypertensive drugs.…”

Section: Introductionmentioning

confidence: 99%

“…Genes that are differentially expressed following treatment with anti-hypertensive drugs may be potential biomarkers and novel targets for the prevention of cardiovascular disease. Moreover, such genes may provide valuable information for the development of new anti-hypertensive therapy ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

The IL-24 gene protects human umbilical vein endothelial cells against H2O2-induced injury and may be useful as a treatment for cardiovascular disease

Wang

Chen

et al. 2016

International Journal of Molecular Medicine

View full text Add to dashboard Cite

The aim of the present study was to investigate the protective effects of interleukin-24 (IL-24) on hydrogen peroxide (H2O2)-induced vascular endothelial injury and to examine the association between IL-24 and cardiovascular disease. Human umbilical vein endothelial cells (HUVECs) were exposed to increasing concentrations of H2O2 in the presence or absence of IL-24, which was introduced via Lipofectamine® 2000-mediated transfection. The successful uptake of the IL-24 plasmid was confirmed by RT-PCR at 24 h post-transfection. The effects of H2O2 and IL-24 on the proliferation and migration of the HUVECs was determined using cell migration assays. Cell viability was determined using a Cell Counting Kit-8 (CCK-8). Apoptosis and the measurement of the intracellular reactive oxygen species (ROS) levels were determined by flow cytometry, and the levels of caspase-3, which is associated with apoptosis, were determined by western blot analysis. Real-time PCR and western blot analysis were also used to measure the levels of multiple cardiovascular disease-associated factors. In vivo experiments were also performed using a rat model of hypertension which was constructed by angiotensin II infusion using an osmotic pump. The mRNA and protein levels of IL-24 were measured in both the control and hypertensive rats; the effects of treatment with enalapril and nifedipine on the IL-24 levels were also examined. Our results revealed that IL-24 protected against the H2O2-mediated abnormal increase in HUVEC proliferation. IL-24 also antagonized H2O2 by reducing the content of ROS in the cells, thus decreasing cellular oxidative damage, improving the cellular survival rate, reducing apoptosis and decreasing the expression of cardiovascular disease-related factors. The results from our in vivo animal experiments revealed that IL-24 expression was lower in the hypertensive rats compared to the healthy controls. Additionally, the IL-24 levels increased following anti-hypertensive therapy. The findings of our study indicate that IL-24 protects against H2O2-mediated endothelial cell damage and may thus provide a novel therapeutic strategy for treatment of cardiovascular disease.

show abstract

“…IL‐24 is secreted by both immune and nonimmune cells. Lee et al found that the expression of IL‐24 decreased in spontaneously hypertensive rats but increased after treatment with antihypertensive drugs . In addition, IL‐24 treatment attenuated the expression of vascular inflammation and hypertension‐related genes in mouse vascular smooth muscle cells, indicating that IL‐24 is a novel therapeutic target for hypertension.…”

mentioning

confidence: 99%

Interleukin 22 Promotes Blood Pressure Elevation and Endothelial Dysfunction in Angiotensin II–Treated Mice

Liu

et al. 2017

JAHA

View full text Add to dashboard Cite

Background CD4+ T helper (Th) cells, including Th1, Th2, and Th17 cells, play critical roles in angiotensin II–induced hypertension. Th22 cells, a novel subset of Th cells, take part in cardiovascular diseases by producing IL‐22 (interleukin 22). This study aimed to investigate whether IL‐22 is involved in hypertension.Methods and ResultsTh22 cells and IL‐22 levels were detected in angiotensin II–infused mice, and the results showed that Th22 cells and IL‐22 levels significantly increased. To determine the effect of Th22/IL‐22 on blood pressure regulation, angiotensin II–infused mice were treated with recombinant mouse IL‐22, an anti–IL‐22 neutralizing monoclonal antibody, or control. Treatment with recombinant IL‐22 resulted in increased blood pressure, amplified inflammatory responses, and aggravated endothelial dysfunction, whereas the anti–IL‐22 neutralizing monoclonal antibody decreased blood pressure, reduced inflammatory responses, and attenuated endothelial dysfunction. To determine whether the STAT3 (signal transducer and activator of transcription 3) pathway mediates the effect of IL‐22 on blood pressure regulation, the special STAT3 pathway inhibitor S31‐201 was administered to mice treated with recombinant IL‐22. S31‐201 treatment significantly ameliorated the IL‐22 effects of increased blood pressure and endothelial dysfunction. In addition, serum IL‐22 levels were significantly increased in hypertensive patients compared with healthy persons. Correlation analysis showed a positive correlation between IL‐22 levels and blood pressure.Conclusions IL‐22 amplifies the inflammatory response, induces endothelial dysfunction and promotes blood pressure elevation in angiotensin II–induced hypertensive mice. The STAT3 pathway mediates the effect of IL‐22 on hypertension. Blocking IL‐22 may be a novel therapeutic strategy to prevent and treat hypertension.

show abstract

Differential gene expression profiles in spontaneously hypertensive rats induced by administration of enalapril and nifedipine

Cited by 11 publications

References 35 publications

Enalapril stimulates collagen biosynthesis through prolidase-dependent mechanism in cultured fibroblasts

Enalapril stimulates collagen biosynthesis through prolidase-dependent mechanism in cultured fibroblasts

The IL-24 gene protects human umbilical vein endothelial cells against H2O2-induced injury and may be useful as a treatment for cardiovascular disease

Interleukin 22 Promotes Blood Pressure Elevation and Endothelial Dysfunction in Angiotensin II–Treated Mice

Contact Info

Product

Resources

About