Renin, Genes, MicroRNAs, and Renal Mechanisms Involved in Hypertension

Morris, Brian J.

doi:10.1161/hypertensionaha.114.04366

Cited by 23 publications

(12 citation statements)

References 131 publications

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“…4 miR-181a and miR-663 were found to target renin, apoptosis-inducing factor mitochondrion-associated 1 (AIFM1) and apolipoprotein E (APOE) mRNAs. 5, 14 11β-hydroxysteroid dehydrogenase type 2 may also be targeted by several miRNAs. 6 …”

Section: Discussionmentioning

confidence: 99%

Endogenous MicroRNAs in Human Microvascular Endothelial Cells Regulate mRNAs Encoded by Hypertension-Related Genes

et al. 2015

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The goal of the present study was to systematically identify endogenous microRNAs in endothelial cells that regulate mRNAs encoded by genes relevant to hypertension. Small RNA deep sequencing was performed in cultured human microvascular endothelial cells. Of the 50 most abundant microRNAs identified, 30 had predicted target mRNAs encoded by genes with known involvement in hypertension or blood pressure regulation. The cells were transfected with anti-miR oligonucleotides to inhibit each of the 30 microRNAs and the mRNA abundance of predicted targets was examined. Of 95 microRNA-target pairs examined, the target mRNAs were significantly up-regulated in 35 pairs and paradoxically down-regulated in 8 pairs. The result indicated significant suppression of the abundance of mRNA encoded by ADM by endogenous miR-181a-5p, ATP2B1 by the miR-27 family, FURIN by miR-125a-5p, FGF5 by the let-7 family, GOSR2 by miR-27a-3p, JAG1 by miR-21-5p, SH2B3 by miR-30a-5p, miR-98, miR-181a-5p, and the miR-125 family, TBX3 by the miR-92 family, ADRA1B by miR-22-3p, ADRA2A by miR-30a-5p and miR-30e-5p, ADRA2B by miR-30e-5p, ADRB1 by the let-7 family and miR-98, EDNRB by the miR-92 family, and NOX4 by the miR-92 family, miR-100-5p, and miR-99b-5p (n=3–9, P<0.05 vs. scrambled anti-miR). Treatment with anti-miR-21 decreased blood pressure in mice fed a 4% NaCl diet. Inhibition of the microRNAs targeting NOX4 mRNA increased H2O2 release from endothelial cells. The findings indicate widespread, tonic control of mRNAs encoded by genes relevant to blood pressure regulation by endothelial microRNAs and provide a novel and uniquely informative basis for studying the role of microRNAs in hypertension.

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Section: Discussionmentioning

confidence: 99%

Endogenous MicroRNAs in Human Microvascular Endothelial Cells Regulate mRNAs Encoded by Hypertension-Related Genes

et al. 2015

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“…A great deal of work over many decades has gone into investigating the role of the circulating reninangiotensin system in preeclampsia. 73 The renin-angiotensin system, which plays a major role in regulating blood pressure, 104 is dysregulated in hypertension. Patients with preeclampsia have lower plasma renin levels 105,106 and higher sensitivity to angiotensin II, 107,108 which predates the appearance of the signs of this pregnancy complication.…”

Section: Research Implicationsmentioning

confidence: 99%

Preeclampsia: novel insights from global RNA profiling of trophoblast subpopulations

Gormley

Ona

Kapidzic

et al. 2017

American Journal of Obstetrics and Gynecology

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BACKGROUND:The maternal signs of preeclampsia, which include the new onset of high blood pressure, can occur because of faulty placentation. We theorized that transcriptomic analyses of trophoblast subpopulations in situ would lend new insights into the role of these cells in preeclampsia pathogenesis. OBJECTIVE: Our goal was to enrich syncytiotrophoblasts, invasive cytotrophoblasts, or endovascular cytotrophoblasts from the placentas of severe preeclampsia cases. Total RNA was subjected to global transcriptional profiling to identify RNAs that were misexpressed compared with controls. STUDY DESIGN: This was a cross-sectional analysis of placentas from women who had been diagnosed with severe preeclampsia. Gestational age-matched controls were placentas from women who had a preterm birth with no signs of infection. Laser microdissection enabled enrichment of syncytiotrophoblasts, invasive cytotrophoblasts, or endovascular cytotrophoblasts. After RNA isolation, a microarray approach was used for global transcriptional profiling. Immunolocalization identified changes in messenger RNA expression that carried over to the protein level. Differential expression of noneprotein-coding RNAs was confirmed by in situ hybridization. A 2-way analysis of variance of non-coding RNA expression identified particular classes that distinguished trophoblasts in cases vs controls. Cajal body foci were visualized by coilin immunolocalization. RESULTS: Comparison of the trophoblast subtype data within each group (severe preeclampsia or noninfected preterm birth) identified many highly differentially expressed genes. They included molecules that are known to be expressed by each subpopulation, which is evidence that the method worked. Genes that were expressed differentially between the 2 groups, in a cell-typeespecific manner, encoded a combination of molecules that previous studies associated with severe preeclampsia and those that were not known to be dysregulated in this pregnancy

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“…The RAS inhibitors such as angiotensin converting enzyme inhibitors (ACEIs) and angiotensin AT1 receptor blockers (ARBs) are widely used in clinical setting . Moreover, renin is secreted by kidneys and catalyzes angiotensinogen to angiotensin I, which is the rate‐limiting and primary step in RAS . Aliskiren, a novel non‐peptide and oral renin inhibitor, directly inhibits plasma renin activity and its enzymatic effects on angiotensinogen .…”

Section: Introductionmentioning

confidence: 99%

Aliskiren protects against myocardial ischaemia‐reperfusion injury via an endothelial nitric oxide synthase dependent manner

Chen

Meng

Wei

et al. 2017

Clin Exp Pharma Physio

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Aliskiren, a direct renin inhibitor, has shown potent ability to attenuate hypertension. Our previous research has found that aliskiren protected against myocardial ischaemia-reperfusion (I/R) injury and enhanced phosphorylation of endothelial nitric oxide synthase (eNOS) in spontaneously hypertensive rats. However, whether the cardioprotective effect of aliskiren against myocardial I/R injury was eNOS-dependent is unknown. In the present study, 12-week-old male eNOS knockout (eNOS ) and wild-type C57BL/6J mice (WT) were orally administrated with the dose of 50 mg/kg per day of aliskiren. After a 4-week treatment, aliskiren decreased blood pressure in eNOS mice, and reduced renin-angiotension II levels in both eNOS and WT mice. Aliskiren also improved left ventricular ejection fraction (EF) and fractional shortening (FS), decreased myocardial infarct size, reduced creatine kinase (CK) and lactate dehydrogenase (LDH) activity in plasma, attenuated dihydroethidium (DHE) fluorescence and levels of malondialdehyde (MDA), enhanced superoxide dismutase (SOD) activity and total antioxidant capacity (T-AOC) in myocardium, increased SOD and thioredoxin (Trx) proteins expression in WT mice subjected to 30 minutes of ischaemia followed by reperfusion for 24 hours. However, aliskiren failed to restore all of the above indices in eNOS mice subjected to the same I/R injury. Our study indicated that aliskiren protected against myocardial I/R injury via an eNOS dependent manner.

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Renin, Genes, MicroRNAs, and Renal Mechanisms Involved in Hypertension

Cited by 23 publications

References 131 publications

Endogenous MicroRNAs in Human Microvascular Endothelial Cells Regulate mRNAs Encoded by Hypertension-Related Genes

Endogenous MicroRNAs in Human Microvascular Endothelial Cells Regulate mRNAs Encoded by Hypertension-Related Genes

Preeclampsia: novel insights from global RNA profiling of trophoblast subpopulations

Aliskiren protects against myocardial ischaemia‐reperfusion injury via an endothelial nitric oxide synthase dependent manner

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