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Gene expression profiling of aortic media after long-term treatment with an angiotensin II-receptor blocker, Losartan

ABSTRACT: Rats (Wag/Rij, females) were chronically treated with Losartan (20mg/d), an angiotensin II-receptor blocker during 9 months. Gene expression profiling was performed on aortic media to understand the long-term effect of this molecule on the cardiovascular system.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE18298 | GEO | 2010/09/23

SECONDARY ACCESSION(S): PRJNA118025

REPOSITORIES: GEO

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Gene expression profiling of aortic media after long-term treatment with an angiotensin II-receptor blocker, Losartan

Project description:Rats (Wag/Rij, females) were chronically treated with Losartan (20mg/d), an angiotensin II-receptor blocker during 9 months. Gene expression profiling was performed on aortic media to understand the long-term effect of this molecule on the cardiovascular system. Two-conditions experiment, Ctrl vs Losartan-treated animals. Biological replicates: 5 control replicates, 5 Losrtan-treated animals. All the RNA samples were pooled to provide a reference RNA for a two-color experiment.

2010-09-23 | E-GEOD-18298 | biostudies-arrayexpress

Losartan controls immune checkpoint blocker-induced edema and improves survival in glioblastoma

Project description:Immune checkpoint blockers (ICBs) have failed in all Phase III glioblastoma trials. Here, we found that ICBs induce cerebral edema in some patients and mice with glioblastoma. Through single-cell RNA sequencing, intravital imaging, and T cell blocking studies in mice, we demonstrated that this edema results from an inflammatory response following anti-PD1 antibody treatment that disrupts the blood-tumor-barrier. Used in lieu of immunosuppressive corticosteroids, the angiotensin receptor blocker losartan prevented this ICB-induced edema and reprogrammed the tumor microenvironment, curing 20% of mice which increased to 40% in combination with standard of care treatment. Using a bihemispheric tumor model, we identified a “hot” tumor immune signature prior to losartan+anti-PD1 therapy that predicted long-term survival. Our findings provide the rationale and associated biomarkers to test losartan with ICBs in glioblastoma patients.

2023-01-01 | GSE212246 | GEO

Attenuation of SARS-CoV-2 Infection by Losartan in Human Kidney Organoids

Project description:COVID-19 associated acute kidney injury (COVID-AKI) is a common complication of SARS-CoV-2 infection in hospitalized patients. It is unclear how susceptible human kidneys are to direct SARS-CoV-2 infection and whether pharmacologic manipulation of the renin-angiotensin II signaling (RAS) pathway modulates this susceptibility. Using induced pluripotent stem cell derived kidney organoids, SARS-CoV-1, SARS-CoV-2 and MERS-CoV tropism, defined by the paired expression of a host receptor (ACE2, NRP1 or DPP4) and protease (TMPRSS2, TMPRSS4, FURIN, CTSB or CTSL), was identified primarily amongst proximal tubule cells. Losartan, an angiotensin II receptor blocker being tested in COVID-19 patients, inhibited angiotensin II mediated internalization of ACE2, upregulated interferon stimulated genes (IFITM1 and BST2) known to restrict viral entry, and attenuated the infection of proximal tubule cells by SARS-CoV-2. Our work highlights the susceptibility of proximal tubule cells to SARS-CoV-2 and reveals a putative protective role for RAS inhibitors during SARS-CoV-2 infection.

2022-01-23 | GSE149687 | GEO

Gene expression regulation by angiotensin II in late gestation fetal sheep

Project description:We undertook a transcriptome-wide discovery approach to provide information on the involved gene regulatory responses to change in fetal cardiac mass in response to chronic infusion of angiotensin II or losartan. One of each of 8 twin fetus pairs was infused with either angiotensin II or losartan daily for five days in utero. A portion of the left ventricular free wall of treatment and control fetuses was excised, homogenized in a reagent, and then total RNA was then isolated and assayed on the agilent microarray

2013-08-09 | E-GEOD-45463 | biostudies-arrayexpress

Dissecting aortic aneurysm in Marfan syndrome is associated with losartan-sensitive transcriptomic modulation of aortic cells

Project description:To improve our limited understanding of the pathogenesis of thoracic aortic aneurysm (TAA) leading to acute aortic dissection, we used single-cell RNA sequencing to profile disease-relevant transcriptomic changes of aortic cell populations in a well-characterized mouse model of the most commonly diagnosed form of Marfan syndrome (MFS). As result,MFSmod were identified only in the aorta of Fbn1mgR/mgR mice. In situ hybridizations of diagnostic transcripts located MFSmod cells to the intima of Fbn1mgR/mgR aortas. Consistent with angiotensin II type I receptor (At1r) contribution to TAA development, MFSmod cells were absent in the aorta of Fbn1mgR/mgR mice treated with the At1r antagonist losartan. Altogether, our findings indicate that a discrete dynamic alteration of aortic cell identity is associated with dissecting TAA in MFS mice and increased risk of aortic dissection in MFS patients.

2023-06-27 | GSE227776 | GEO

Transcriptomic profiling of Angiotensin II induced fibrotic myocardial tissue in response to EHP-101 or Losartan

Project description:In order to obtain a global perspective of the effect of EHP-101 and Losartan on cardiac fibrosis, we performed a mRNA-Seq analysis of the myocardial tissue changes in response to Ang II, Ang II + EHP-101 and Ang II + Losartan.

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RNA sequencing of lung tissue from Angiotensin2/TRV023/losartan treated MCT rats

Project description:We report the application of RNA sequencing in lung tissues of MCT rats, that were treated with Angiotensin 2 or TRV023 or Losartan to study their effects on Pulmonary hypertension. We received FPKM data of each gene from each group of MCT rats. The gene expression of the study MCT rats were normalized to control MCT rat. The differentially expressed genes in Angiotensin 2 and TRV023 treated MCT rats, confirmed that like Angiotensin 2, TRV023 is also involved in vascular remodelling and lead to worsening of pulmonary hypertension.

2021-09-08 | GSE183339 | GEO

Gene expression regulation by angiotensin II in late gestation fetal sheep

2013-08-09 | GSE45463 | GEO

Angiotensin receptor blocker Losartan inhibits tumor growth of colorectal cancer.

Project description: Not available

| S-EPMC8056058 | biostudies-literature

LRP1 in Vascular Remodeling and Angiotensin Signaling

Project description:Vascular smooth muscle cells (vSMC) exert a critical role in sensing and maintaining vascular integrity. These cells abundantly express the low-density lipoprotein receptor-related protein 1 (LRP1), a large endocytic and signaling receptor that recognizes numerous ligands including ApoE-rich lipoproteins, proteases, and protease-inhibitor complexes. We observed the spontaneous formation of aneurysms in the superior mesenteric artery (SMA) of both male and female mice in which LRP1 was genetically deleted in v SMC (smLRP1-/- mice). Quantitative proteomics revealed elevated abundance of several proteins in smLRP1-/- mice that are known to be induced by angiotensin II (AngII)-mediated signaling, suggesting that this pathway is dysregulated. Administration of losartan, an AngII type I receptor antagonist, or an angiotensinogen antisense oligonucleotide to reduce plasma angiotensinogen concentrations restored the normal SMA phenotype in smLRP1-/- mice and prevented aneurysm formation. Additionally, employing a vascular injury model, we noted excessive vascular remodeling and neointima formation in smLRP1-/- mice that was restored by losartan administration. Together, these findings reveal that LRP1 regulates vascular integrity and remodeling of the SMA by attenuating excessive AngII-mediated signaling.

2023-03-11 | PXD038236 | Pride

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