Evidence map›Paper›PMID 26781283›Full record

ArticleHypertension (Dallas, Tex. : 1979)2016

Rnd3/RhoE Modulates Hypoxia-Inducible Factor 1α/Vascular Endothelial Growth Factor Signaling by Stabilizing Hypoxia-Inducible Factor 1α and Regulates Responsive Cardiac Angiogenesis.

Xiaojing Yue, Xi Lin, Tingli Yang, Xiangsheng Yang, Xin Yi, Xuejun Jiang, Xiaoyan Li, Tianfa Li, Junli Guo, Yuan Dai and 7 more

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

Article in Hypertension (Dallas, Tex. : 1979), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.6field-weighted citation impact, top 11% 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

30 citing papers in PubMed, 48 citations in OpenAlex.

  1. Molecular Mechanisms Governing Vascular Function in Heart Failure.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Review
  2. Review
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  10. Maternal RND3/RhoE deficiency impairs placental mitochondrial function in preeclampsia by modulating the PPARγ-UCP2 cascade.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
    Article
  11. MiR-221-3p targets Hif-1α to inhibit angiogenesis in heart failure.Laboratory investigation; a journal of technical methods and pathology · 2021
    Article
  12. Article
  13. Article
  14. Article
  15. Tipifarnib as a Precision Therapy forMolecular cancer therapeutics · 2020
    Article
  16. Article
  17. BioMed research international · 2020
    Article
  18. Review
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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

17 authors at 7 institutions in 2 countries.

Xiaojing YueFrom the Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (X.Y., Y.Y.); Texas A&M University Health Science Center, Institute of Biosciences and Technology, Houston (X.Y., X.L., T.Y., X.Y., Y.D., K.C.A., J.C.); Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (X.Y., X.J., X.L.); Cardiovascular Disease and Research Institute, Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (T.L., J.G.); Department of Pediatrics, Indiana University School of Medicine, Indianapolis (J.S., L.W.); and Methodist DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, TX (K.A.Y., G.T.-A.).
Xi LinFrom the Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (X.Y., Y.Y.); Texas A&M University Health Science Center, Institute of Biosciences and Technology, Houston (X.Y., X.L., T.Y., X.Y., Y.D., K.C.A., J.C.); Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (X.Y., X.J., X.L.); Cardiovascular Disease and Research Institute, Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (T.L., J.G.); Department of Pediatrics, Indiana University School of Medicine, Indianapolis (J.S., L.W.); and Methodist DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, TX (K.A.Y., G.T.-A.).
Tingli YangFrom the Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (X.Y., Y.Y.); Texas A&M University Health Science Center, Institute of Biosciences and Technology, Houston (X.Y., X.L., T.Y., X.Y., Y.D., K.C.A., J.C.); Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (X.Y., X.J., X.L.); Cardiovascular Disease and Research Institute, Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (T.L., J.G.); Department of Pediatrics, Indiana University School of Medicine, Indianapolis (J.S., L.W.); and Methodist DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, TX (K.A.Y., G.T.-A.).
Xiangsheng YangFrom the Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (X.Y., Y.Y.); Texas A&M University Health Science Center, Institute of Biosciences and Technology, Houston (X.Y., X.L., T.Y., X.Y., Y.D., K.C.A., J.C.); Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (X.Y., X.J., X.L.); Cardiovascular Disease and Research Institute, Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (T.L., J.G.); Department of Pediatrics, Indiana University School of Medicine, Indianapolis (J.S., L.W.); and Methodist DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, TX (K.A.Y., G.T.-A.).
Xin YiFrom the Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (X.Y., Y.Y.); Texas A&M University Health Science Center, Institute of Biosciences and Technology, Houston (X.Y., X.L., T.Y., X.Y., Y.D., K.C.A., J.C.); Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (X.Y., X.J., X.L.); Cardiovascular Disease and Research Institute, Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (T.L., J.G.); Department of Pediatrics, Indiana University School of Medicine, Indianapolis (J.S., L.W.); and Methodist DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, TX (K.A.Y., G.T.-A.).
Xuejun JiangFrom the Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (X.Y., Y.Y.); Texas A&M University Health Science Center, Institute of Biosciences and Technology, Houston (X.Y., X.L., T.Y., X.Y., Y.D., K.C.A., J.C.); Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (X.Y., X.J., X.L.); Cardiovascular Disease and Research Institute, Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (T.L., J.G.); Department of Pediatrics, Indiana University School of Medicine, Indianapolis (J.S., L.W.); and Methodist DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, TX (K.A.Y., G.T.-A.).
Xiaoyan LiFrom the Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (X.Y., Y.Y.); Texas A&M University Health Science Center, Institute of Biosciences and Technology, Houston (X.Y., X.L., T.Y., X.Y., Y.D., K.C.A., J.C.); Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (X.Y., X.J., X.L.); Cardiovascular Disease and Research Institute, Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (T.L., J.G.); Department of Pediatrics, Indiana University School of Medicine, Indianapolis (J.S., L.W.); and Methodist DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, TX (K.A.Y., G.T.-A.).
Tianfa LiFrom the Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (X.Y., Y.Y.); Texas A&M University Health Science Center, Institute of Biosciences and Technology, Houston (X.Y., X.L., T.Y., X.Y., Y.D., K.C.A., J.C.); Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (X.Y., X.J., X.L.); Cardiovascular Disease and Research Institute, Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (T.L., J.G.); Department of Pediatrics, Indiana University School of Medicine, Indianapolis (J.S., L.W.); and Methodist DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, TX (K.A.Y., G.T.-A.).
Junli GuoFrom the Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (X.Y., Y.Y.); Texas A&M University Health Science Center, Institute of Biosciences and Technology, Houston (X.Y., X.L., T.Y., X.Y., Y.D., K.C.A., J.C.); Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (X.Y., X.J., X.L.); Cardiovascular Disease and Research Institute, Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (T.L., J.G.); Department of Pediatrics, Indiana University School of Medicine, Indianapolis (J.S., L.W.); and Methodist DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, TX (K.A.Y., G.T.-A.).
Yuan DaiFrom the Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (X.Y., Y.Y.); Texas A&M University Health Science Center, Institute of Biosciences and Technology, Houston (X.Y., X.L., T.Y., X.Y., Y.D., K.C.A., J.C.); Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (X.Y., X.J., X.L.); Cardiovascular Disease and Research Institute, Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (T.L., J.G.); Department of Pediatrics, Indiana University School of Medicine, Indianapolis (J.S., L.W.); and Methodist DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, TX (K.A.Y., G.T.-A.).
Jianjian ShiFrom the Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (X.Y., Y.Y.); Texas A&M University Health Science Center, Institute of Biosciences and Technology, Houston (X.Y., X.L., T.Y., X.Y., Y.D., K.C.A., J.C.); Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (X.Y., X.J., X.L.); Cardiovascular Disease and Research Institute, Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (T.L., J.G.); Department of Pediatrics, Indiana University School of Medicine, Indianapolis (J.S., L.W.); and Methodist DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, TX (K.A.Y., G.T.-A.).
Lei WeiFrom the Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (X.Y., Y.Y.); Texas A&M University Health Science Center, Institute of Biosciences and Technology, Houston (X.Y., X.L., T.Y., X.Y., Y.D., K.C.A., J.C.); Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (X.Y., X.J., X.L.); Cardiovascular Disease and Research Institute, Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (T.L., J.G.); Department of Pediatrics, Indiana University School of Medicine, Indianapolis (J.S., L.W.); and Methodist DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, TX (K.A.Y., G.T.-A.).
Keith A YoukerFrom the Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (X.Y., Y.Y.); Texas A&M University Health Science Center, Institute of Biosciences and Technology, Houston (X.Y., X.L., T.Y., X.Y., Y.D., K.C.A., J.C.); Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (X.Y., X.J., X.L.); Cardiovascular Disease and Research Institute, Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (T.L., J.G.); Department of Pediatrics, Indiana University School of Medicine, Indianapolis (J.S., L.W.); and Methodist DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, TX (K.A.Y., G.T.-A.).
Guillermo Torre-AmioneFrom the Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (X.Y., Y.Y.); Texas A&M University Health Science Center, Institute of Biosciences and Technology, Houston (X.Y., X.L., T.Y., X.Y., Y.D., K.C.A., J.C.); Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (X.Y., X.J., X.L.); Cardiovascular Disease and Research Institute, Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (T.L., J.G.); Department of Pediatrics, Indiana University School of Medicine, Indianapolis (J.S., L.W.); and Methodist DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, TX (K.A.Y., G.T.-A.).
Yanhong YuFrom the Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (X.Y., Y.Y.); Texas A&M University Health Science Center, Institute of Biosciences and Technology, Houston (X.Y., X.L., T.Y., X.Y., Y.D., K.C.A., J.C.); Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (X.Y., X.J., X.L.); Cardiovascular Disease and Research Institute, Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (T.L., J.G.); Department of Pediatrics, Indiana University School of Medicine, Indianapolis (J.S., L.W.); and Methodist DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, TX (K.A.Y., G.T.-A.).
Kelsey C AndradeFrom the Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (X.Y., Y.Y.); Texas A&M University Health Science Center, Institute of Biosciences and Technology, Houston (X.Y., X.L., T.Y., X.Y., Y.D., K.C.A., J.C.); Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (X.Y., X.J., X.L.); Cardiovascular Disease and Research Institute, Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (T.L., J.G.); Department of Pediatrics, Indiana University School of Medicine, Indianapolis (J.S., L.W.); and Methodist DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, TX (K.A.Y., G.T.-A.).
Jiang ChangFrom the Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (X.Y., Y.Y.); Texas A&M University Health Science Center, Institute of Biosciences and Technology, Houston (X.Y., X.L., T.Y., X.Y., Y.D., K.C.A., J.C.); Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (X.Y., X.J., X.L.); Cardiovascular Disease and Research Institute, Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (T.L., J.G.); Department of Pediatrics, Indiana University School of Medicine, Indianapolis (J.S., L.W.); and Methodist DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, TX (K.A.Y., G.T.-A.). jchang@ibt.tamhsc.edu.
Hainan Medical College Hospital · CNNanfang Hospital · CNWuhan University · CNIndiana University – Purdue University Indianapolis · USIndiana University School of MedicineRenmin Hospital of Wuhan University · CNSouthern Medical University · CN

Funding

Fibrogenic Role of ROCK delta1 and Mechanism in Cardiac RemodelingR01HL102314 · NHLBI · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI CHANG, JIANG · 2010 to 2014
$1.8M
Mechanistic Role of Rnd3 in Response to Cardiac StressR01HL123953 · NHLBI · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI CHANG, JIANG · 2014 to 2017
$1.7M
Regulation of cardiac stress responses by Rho kinaseR01HL107537 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI WEI, LEI · 2013 to 2016
$1.5M
Mechanism of SRF-N-mediated Cardiac SuppressionK02HL098956 · NHLBI · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI CHANG, JIANG · 2010 to 2014
$471k
NHLBI NIH HHS K02 HL098956NHLBI NIH HHS K02HL098956NHLBI NIH HHS R01 HL102314NHLBI NIH HHS R01HL102314NHLBI NIH HHS R01 HL107537NHLBI NIH HHS R01 HL123953NHLBI NIH HHS R01HL123953
6 · The paper itself

Abstract

The insufficiency of compensatory angiogenesis in the heart of patients with hypertension contributes to heart failure transition. The hypoxia-inducible factor 1α-vascular endothelial growth factor (HIF1α-VEGF) signaling cascade controls responsive angiogenesis. One of the challenges in reprograming the insufficient angiogenesis is to achieve a sustainable tissue exposure to the proangiogenic factors, such as HIF1α stabilization. In this study, we identified Rnd3, a small Rho GTPase, as a proangiogenic factor participating in the regulation of the HIF1α-VEGF signaling cascade. Rnd3 physically interacted with and stabilized HIF1α, and consequently promoted VEGFA expression and endothelial cell tube formation. To demonstrate this proangiogenic role of Rnd3 in vivo, we generated Rnd3 knockout mice. Rnd3 haploinsufficient (Rnd3(+/-)) mice were viable, yet developed dilated cardiomyopathy with heart failure after transverse aortic constriction stress. The poststress Rnd3(+/-) hearts showed significantly impaired angiogenesis and decreased HIF1α and VEGFA expression. The angiogenesis defect and heart failure phenotype were partially rescued by cobalt chloride treatment, a HIF1α stabilizer, confirming a critical role of Rnd3 in stress-responsive angiogenesis. Furthermore, we generated Rnd3 transgenic mice and demonstrated that Rnd3 overexpression in heart had a cardioprotective effect through reserved cardiac function and preserved responsive angiogenesis after pressure overload. Finally, we assessed the expression levels of Rnd3 in the human heart and detected significant downregulation of Rnd3 in patients with end-stage heart failure. We concluded that Rnd3 acted as a novel proangiogenic factor involved in cardiac responsive angiogenesis through HIF1α-VEGFA signaling promotion. Rnd3 downregulation observed in patients with heart failure may explain the insufficient compensatory angiogenesis involved in the transition to heart failure.

Indexed as

Gene Expression RegulationAnimalsBlotting, WesternCoronary VesselsDisease Models, AnimalEndothelium, VascularHumansHypertensionHypoxia-Inducible Factor 1, alpha SubunitMiceMice, KnockoutMice, TransgenicNeovascularization, Pathologicrho GTP-Binding ProteinsRNASignal TransductionHypoxia-Inducible Factor 1, alpha Subunitrho GTP-Binding ProteinsRNARnd3 protein, mouseVascular Endothelial Growth Factor Aangiogenesis factorG-proteinheart failurehypertensionhypertrophyvascular endothelial growth factor A

Identifiers

PMID26781283
PMCPMC4752414
OpenAlexW2272914800

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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.