Evidence map›Paper›PMID 25225206›Full record

ArticleHypertension (Dallas, Tex. : 1979)2014

Oral delivery of Angiotensin-converting enzyme 2 and Angiotensin-(1-7) bioencapsulated in plant cells attenuates pulmonary hypertension.

Vinayak Shenoy, Kwang-Chul Kwon, Anandharajan Rathinasabapathy, Shina Lin, Guiying Jin, Chunjuan Song, Pollob Shil, Anand Nair, Yanfei Qi, Qiuhong Li and 4 more

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 81 papers.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed
10.1field-weighted citation impact, top 1% 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

81 citing papers in PubMed, 142 citations in OpenAlex.

  1. Trial
  2. Article
  3. Emerging Concepts in Therapeutic Interventions for Idiopathic Pulmonary Fibrosis.Seminars in respiratory and critical care medicine · 2025
    Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Association Between ACE2 and Lung Diseases.Infection and drug resistance · 2024
    Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Insights into plastome ofSaudi journal of biological sciences · 2022
    Article
  19. A Pair of "ACEs".Journal of dental research · 2022
    Review
  20. Review

21 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 1 institution in 1 country.

Vinayak ShenoyDepartments of Pharmacodynamics (V.S., A.R., M.J.K.), Physiology and Functional Genomics (C.S., Y.Q., M.K.R.), and Ophthalmology (P.S., Q.L.), University of Florida, Gainesville; Departments of Biochemistry and Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia (K.-C.K., S.L., G.J., H.D.); and Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge (A.N., J.F.).
Kwang-Chul KwonDepartments of Pharmacodynamics (V.S., A.R., M.J.K.), Physiology and Functional Genomics (C.S., Y.Q., M.K.R.), and Ophthalmology (P.S., Q.L.), University of Florida, Gainesville; Departments of Biochemistry and Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia (K.-C.K., S.L., G.J., H.D.); and Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge (A.N., J.F.).
Anandharajan RathinasabapathyDepartments of Pharmacodynamics (V.S., A.R., M.J.K.), Physiology and Functional Genomics (C.S., Y.Q., M.K.R.), and Ophthalmology (P.S., Q.L.), University of Florida, Gainesville; Departments of Biochemistry and Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia (K.-C.K., S.L., G.J., H.D.); and Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge (A.N., J.F.).
Shina LinDepartments of Pharmacodynamics (V.S., A.R., M.J.K.), Physiology and Functional Genomics (C.S., Y.Q., M.K.R.), and Ophthalmology (P.S., Q.L.), University of Florida, Gainesville; Departments of Biochemistry and Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia (K.-C.K., S.L., G.J., H.D.); and Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge (A.N., J.F.).
Guiying JinDepartments of Pharmacodynamics (V.S., A.R., M.J.K.), Physiology and Functional Genomics (C.S., Y.Q., M.K.R.), and Ophthalmology (P.S., Q.L.), University of Florida, Gainesville; Departments of Biochemistry and Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia (K.-C.K., S.L., G.J., H.D.); and Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge (A.N., J.F.).
Chunjuan SongDepartments of Pharmacodynamics (V.S., A.R., M.J.K.), Physiology and Functional Genomics (C.S., Y.Q., M.K.R.), and Ophthalmology (P.S., Q.L.), University of Florida, Gainesville; Departments of Biochemistry and Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia (K.-C.K., S.L., G.J., H.D.); and Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge (A.N., J.F.).
Pollob ShilDepartments of Pharmacodynamics (V.S., A.R., M.J.K.), Physiology and Functional Genomics (C.S., Y.Q., M.K.R.), and Ophthalmology (P.S., Q.L.), University of Florida, Gainesville; Departments of Biochemistry and Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia (K.-C.K., S.L., G.J., H.D.); and Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge (A.N., J.F.).
Anand NairDepartments of Pharmacodynamics (V.S., A.R., M.J.K.), Physiology and Functional Genomics (C.S., Y.Q., M.K.R.), and Ophthalmology (P.S., Q.L.), University of Florida, Gainesville; Departments of Biochemistry and Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia (K.-C.K., S.L., G.J., H.D.); and Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge (A.N., J.F.).
Yanfei QiDepartments of Pharmacodynamics (V.S., A.R., M.J.K.), Physiology and Functional Genomics (C.S., Y.Q., M.K.R.), and Ophthalmology (P.S., Q.L.), University of Florida, Gainesville; Departments of Biochemistry and Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia (K.-C.K., S.L., G.J., H.D.); and Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge (A.N., J.F.).
Qiuhong LiDepartments of Pharmacodynamics (V.S., A.R., M.J.K.), Physiology and Functional Genomics (C.S., Y.Q., M.K.R.), and Ophthalmology (P.S., Q.L.), University of Florida, Gainesville; Departments of Biochemistry and Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia (K.-C.K., S.L., G.J., H.D.); and Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge (A.N., J.F.).
Joseph FrancisDepartments of Pharmacodynamics (V.S., A.R., M.J.K.), Physiology and Functional Genomics (C.S., Y.Q., M.K.R.), and Ophthalmology (P.S., Q.L.), University of Florida, Gainesville; Departments of Biochemistry and Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia (K.-C.K., S.L., G.J., H.D.); and Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge (A.N., J.F.).
Michael J KatovichDepartments of Pharmacodynamics (V.S., A.R., M.J.K.), Physiology and Functional Genomics (C.S., Y.Q., M.K.R.), and Ophthalmology (P.S., Q.L.), University of Florida, Gainesville; Departments of Biochemistry and Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia (K.-C.K., S.L., G.J., H.D.); and Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge (A.N., J.F.).
Henry DaniellDepartments of Pharmacodynamics (V.S., A.R., M.J.K.), Physiology and Functional Genomics (C.S., Y.Q., M.K.R.), and Ophthalmology (P.S., Q.L.), University of Florida, Gainesville; Departments of Biochemistry and Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia (K.-C.K., S.L., G.J., H.D.); and Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge (A.N., J.F.). hdaniell@upenn.edu mraizada@ufl.edu.
Mohan K RaizadaDepartments of Pharmacodynamics (V.S., A.R., M.J.K.), Physiology and Functional Genomics (C.S., Y.Q., M.K.R.), and Ophthalmology (P.S., Q.L.), University of Florida, Gainesville; Departments of Biochemistry and Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia (K.-C.K., S.L., G.J., H.D.); and Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge (A.N., J.F.). hdaniell@upenn.edu mraizada@ufl.edu.
University of Pennsylvania · US

Funding

Oral immune modulatory therapy using antigens bioencapsulated in plant cellsR01HL107904 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DANIELL, HENRY · 2011 to 2023
$7.5M
Angiotensin-Converting Enzyme2 in Vascular Endothelial FunctionR01HL102033 · NHLBI · UNIVERSITY OF FLORIDA · PI RAIZADA, MOHAN K. · 2010 to 2019
$4.3M
Oral Therapy for Hemophilia AR01HL109442 · NHLBI · UNIVERSITY OF FLORIDA · PI DANIELL, HENRY, HERZOG, ROLAND W. · 2011 to 2015
$3.5M
Vision Research CoreP30EY021721 · NEI · UNIVERSITY OF FLORIDA · PI HAUSWIRTH, WILLIAM W · 2011 to 2015
$2.8M
Expression of Human Therapeutic Proteins in Transgenic Tobacco ChloroplastsR01GM063879 · NIGMS · UNIVERSITY OF CENTRAL FLORIDA · PI DANIELL, HENRY · 2002 to 2010
$2.0M
Ocular Renin Angiotensin System in Pathogenesis of Diabetic RetinopathyR01EY021752 · NEI · UNIVERSITY OF FLORIDA · PI LI, QIUHONG · 2012 to 2015
$1.4M
ACE2 as a target for pulmonary hypertension therapeuticsRC1HL099980 · NHLBI · UNIVERSITY OF FLORIDA · PI GRANT, MARIA BARTOLOMEO, RAIZADA, MOHAN K. · 2009 to 2010
$982k
NEI NIH HHS EY021752NEI NIH HHS P30 EY021721NEI NIH HHS R01 EY021752NHLBI NIH HHS HL099980NHLBI NIH HHS HL102033NHLBI NIH HHS HL106687NHLBI NIH HHS HL109442NHLBI NIH HHS R01 HL102033NHLBI NIH HHS R01 HL107904NHLBI NIH HHS R01 HL109442NHLBI NIH HHS RC1 HL099980NIGMS NIH HHS R01 GM063879
6 · The paper itself

Abstract

Emerging evidences indicate that diminished activity of the vasoprotective axis of the renin-angiotensin system, constituting angiotensin-converting enzyme 2 (ACE2) and its enzymatic product, angiotensin-(1-7) [Ang-(1-7)] contribute to the pathogenesis of pulmonary hypertension (PH). However, long-term repetitive delivery of ACE2 or Ang-(1-7) would require enhanced protein stability and ease of administration to improve patient compliance. Chloroplast expression of therapeutic proteins enables their bioencapsulation within plant cells to protect against gastric enzymatic degradation and facilitates long-term storage at room temperature. Besides, fusion to a transmucosal carrier helps effective systemic absorption from the intestine on oral delivery. We hypothesized that bioencapsulating ACE2 or Ang-(1-7) fused to the cholera nontoxin B subunit would enable development of an oral delivery system that is effective in treating PH. PH was induced in male Sprague Dawley rats by monocrotaline administration. Subset of animals was simultaneously treated with bioencapsulaed ACE2 or Ang-(1-7) (prevention protocol). In a separate set of experiments, drug treatment was initiated after 2 weeks of PH induction (reversal protocol). Oral feeding of rats with bioencapsulated ACE2 or Ang-(1-7) prevented the development of monocrotaline-induced PH and improved associated cardiopulmonary pathophysiology. Furthermore, in the reversal protocol, oral ACE2 or Ang-(1-7) treatment significantly arrested disease progression, along with improvement in right heart function, and decrease in pulmonary vessel wall thickness. In addition, a combination therapy with ACE2 and Ang-(1-7) augmented the beneficial effects against monocrotaline-induced lung injury. Our study provides proof-of-concept for a novel low-cost oral ACE2 or Ang-(1-7) delivery system using transplastomic technology for pulmonary disease therapeutics.

Indexed as

Administration, OralAngiotensin-Converting Enzyme 2Angiotensin IAnimalsAntihypertensive AgentsBlood PressureChloroplastsDisease Models, AnimalDose-Response Relationship, DrugDrug CarriersDrug Therapy, CombinationHypertension, PulmonaryMalePeptide FragmentsPeptidyl-Dipeptidase ARatsAce2 protein, ratAngiotensin-Converting Enzyme 2Angiotensin Iangiotensin I (1-7)Antihypertensive AgentsDrug CarriersPeptide FragmentsPeptidyl-Dipeptidase Achloroplastmolecular farmingplant-made pharmaceuticalspulmonary hypertensionrenin–angiotensin system

Identifiers

PMID25225206
PMCPMC4239698
OpenAlexW2104188024

What OpenQuestion holds

Textmetadata
LicenceTDM
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.