Evidence map›Paper›PMID 36082235›Full record

ArticlePNAS nexus2022

Nature-inspired delivery of mitochondria-targeted angiotensin receptor blocker.

Jude M Phillip, Ran Lin, Andrew Cheetham, David Stern, Yukang Li, Yuzhu Wang, Han Wang, David Rini, Honggang Cui, Jeremy D Walston and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PNAS nexus, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.4field-weighted citation impact, top 41% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 6 citations in OpenAlex.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Jude M PhillipDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.ORCID https://orcid.org/0000-0002-2999-5254
Ran LinDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
Andrew CheethamDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
David SternDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
Yukang LiInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA.
Yuzhu WangDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
Han WangDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
David RiniDepartment of Art as Applied to Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Honggang CuiDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.ORCID https://orcid.org/0000-0002-4684-2655
Jeremy D WalstonDepartment of Medicine, Division of Geriatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID https://orcid.org/0000-0002-6965-2723
Peter M AbadirDepartment of Medicine, Division of Geriatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID https://orcid.org/0000-0002-8186-0066
Johns Hopkins University · US

Funding

Technological Assessment and Solutions Core - RC4P30AG021334 · NIA · JOHNS HOPKINS UNIVERSITY · PI Jeremy D Walston · 2003 to 2026
$33.2M
Age Related Change in Mitochondrial Angiotensin System and Mitochondrial DeclineR01AG046441 · NIA · JOHNS HOPKINS UNIVERSITY · PI ABADIR, PETER M. · 2014 to 2018
$2.3M
NIA NIH HHS P30 AG021334NIA NIH HHS R01 AG046441
6 · The paper itself

Abstract

Mitochondria are critical regulators of cellular function and survival. We have previously demonstrated that functional angiotensin receptors embedded within the inner mitochondrial membrane modulate mitochondrial energy production and free radical generation. The expression of mitochondrial angiotensin II type-1 receptors increases during aging, with a complementary decrease in angiotensin II type-2 receptor density. To address this age-associated mitochondrial dysfunction, we have developed a mitochondria-targeted delivery system to effectively transport angiotensin type-1 receptor blocker-Losartan (mtLOS) into the inner mitochondrial membrane. We engineered mtLOS to become active within the mitochondria after cleavage by mitochondrial peptidases. Our data demonstrate effective and targeted delivery of mtLOS into the mitochondria, compared to a free Losartan, or Losartan conjugated to a scrambled mitochondrial target signal peptide, with significant shifts in mitochondrial membrane potential upon mtLOS treatment. Furthermore, engineered mitochondrial-targeting modalities could open new avenues to transport nonmitochondrial proteins into the mitochondria, such as other macromolecules and therapeutic agents.

Indexed as

angiotensin systemLosartanmitochondriamitochondrial targeting

Identifiers

PMID36082235
PMCPMC9437577
OpenAlexW4289890808

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.