ArticleJCI insight2019
Loss of smooth muscle CYB5R3 amplifies angiotensin II-induced hypertension by increasing sGC heme oxidation.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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.
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Who cites it
23 citing papers in PubMed, 52 citations in OpenAlex.
- Mitoregulin supports mitochondrial membrane integrity and protects against cardiac ischaemia-reperfusion injury.Cardiovascular research · 2026Article
- Pressure Myography and Cardiac Flow Simulator for Mechanical Characterization of Native and Engineered Blood Vessels.Device · 2026Article
- Beta arrestin 1 is a key regulator of pulmonary vascular tone.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Endothelial CYB5R3 couples store-operated calcium entry to TRPV2 activation and vascular fitness.bioRxiv : the preprint server for biology · 2025Article
- Soluble guanylate cyclase stimulators and activators as potential antihypertensive drugs.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Review
- Sex-dependent adaptations in heart mitochondria from transgenic mice overexpressing cytochrome bMitochondrion · 2025Article
- CYB5R3 T117S tempers fetal hemoglobin induction by hydroxyurea in patients with sickle cell disease.Blood advances · 2024Article
- Potentiation of BKCa channels by cystic fibrosis transmembrane conductance regulator correctors VX-445 and VX-121.The Journal of clinical investigation · 2024Article
- Bedding as a variable affecting fasting blood glucose and vascular physiology in mice.American journal of physiology. Heart and circulatory physiology · 2023Article
- CYB5R3 in type II alveolar epithelial cells protects against lung fibrosis by suppressing TGF-β1 signaling.JCI insight · 2023Article
- Cellular Factors That Shape the Activity or Function of Nitric Oxide-Stimulated Soluble Guanylyl Cyclase.Cells · 2023Review
- Bioinformatics Analysis of Next Generation Sequencing Data Identifies Molecular Biomarkers Associated With Type 2 Diabetes Mellitus.Clinical medicine insights. Endocrinology and diabetes · 2023Article
- Inhaled mosliciguat (BAY 1237592): targeting pulmonary vasculature via activating apo-sGC.Respiratory research · 2022Article
- Loss of cardiomyocyte CYB5R3 impairs redox equilibrium and causes sudden cardiac death.The Journal of clinical investigation · 2022Article
- Soluble guanylate cyclase activator BAY 54-6544 improves vasomotor function and survival in an accelerated ageing mouse model.Aging cell · 2022Article
- Benign prostatic hyperplasia/obstruction ameliorated using a soluble guanylate cyclase activator.The Journal of pathology · 2022Article
- Smooth muscle cell CYB5R3 preserves cardiac and vascular function under chronic hypoxic stress.Journal of molecular and cellular cardiology · 2022Article
- Cooperation between CYB5R3 and NOX4 via coenzyme Q mitigates endothelial inflammation.Redox biology · 2021Article
- Redox Switches Controlling Nitric Oxide Signaling in the Resistance Vasculature and Implications for Blood Pressure Regulation: Mid-Career Award for Research Excellence 2020.Hypertension (Dallas, Tex. : 1979) · 2021Review
- Hydrogen Sulfide: Novel Endogenous and Exogenous Modulator of Oxidative Stress in Retinal Degeneration Diseases.Molecules (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Nitric oxide regulates BP by binding the reduced heme iron (Fe2+) in soluble guanylyl cyclase (sGC) and relaxing vascular smooth muscle cells (SMCs). We previously showed that sGC heme iron reduction (Fe3+ → Fe2+) is modulated by cytochrome b5 reductase 3 (CYB5R3). However, the in vivo role of SMC CYB5R3 in BP regulation remains elusive. Here, we generated conditional smooth muscle cell-specific Cyb5r3 KO mice (SMC CYB5R3-KO) to test if SMC CYB5R3 loss affects systemic BP in normotension and hypertension via regulation of the sGC redox state. SMC CYB5R3-KO mice exhibited a 5.84-mmHg increase in BP and impaired acetylcholine-induced vasodilation in mesenteric arteries compared with controls. To drive sGC oxidation and elevate BP, we infused mice with angiotensin II. We found that SMC CYB5R3-KO mice exhibited a 14.75-mmHg BP increase, and mesenteric arteries had diminished nitric oxide-dependent vasodilation but increased responsiveness to sGC heme-independent activator BAY 58-2667 over controls. Furthermore, acute injection of BAY 58-2667 in angiotensin II-treated SMC CYB5R3-KO mice showed greater BP reduction compared with controls. Together, these data provide the first in vivo evidence to our knowledge that SMC CYB5R3 is an sGC heme reductase in resistance arteries and provides resilience against systemic hypertension development.
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Registered trials
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.