ArticleThe Journal of clinical investigation2006
Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels.
Article in The Journal of clinical investigation, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 221 papers.
What it found
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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.
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.
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Who cites it
221 citing papers in PubMed, 445 citations in OpenAlex.
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- Molecular damage associated with ageing drives inflammation in cardiovascular disease.Nature reviews. Cardiology · 2026Review
- Cytochrome bBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Regulatory interplay between nitric oxide and heme in redox signaling and inflammation.Redox biology · 2026Review
- 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
- NO-cGMP Signaling in Endothelial Function of the Healthy and Inflamed Dental Pulp.International journal of molecular sciences · 2025Review
- Impact of Endothelial Diversity and Dysfunction on Cardiovascular Disease.Comprehensive Physiology · 2025Review
- 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
- The αInternational journal of molecular sciences · 2024Article
- Nitric Oxide Signaling and Sensing in Age-Related Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Soluble guanylate cyclase stimulators and activators: new horizons in the treatment of priapism associated with sickle cell disease.Frontiers in pharmacology · 2024Review
- Renal and Vascular Functional Decline in Aged Low Birth Weight Murine Adults.Kidney & blood pressure research · 2024Article
- Promising Cerebral Blood Flow Enhancers in Acute Ischemic Stroke.Translational stroke research · 2023Review
- The FDA's New Guideline "Generally Accepted Scientific Knowledge" (GASK): An Opportunity to Expedite the Approval of Biosimilars.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Thiol-catalyzed formation of NO-ferroheme regulates intravascular NO signaling.Nature chemical biology · 2023Article
- Review
161 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ROS are a risk factor of several cardiovascular disorders and interfere with NO/soluble guanylyl cyclase/cyclic GMP (NO/sGC/cGMP) signaling through scavenging of NO and formation of the strong oxidant peroxynitrite. Increased oxidative stress affects the heme-containing NO receptor sGC by both decreasing its expression levels and impairing NO-induced activation, making vasodilator therapy with NO donors less effective. Here we show in vivo that oxidative stress and related vascular disease states, including human diabetes mellitus, led to an sGC that was indistinguishable from the in vitro oxidized/heme-free enzyme. This sGC variant represents what we believe to be a novel cGMP signaling entity that is unresponsive to NO and prone to degradation. Whereas high-affinity ligands for the unoccupied heme pocket of sGC such as zinc-protoporphyrin IX and the novel NO-independent sGC activator 4-[((4-carboxybutyl){2-[(4-phenethylbenzyl)oxy]phenethyl}amino) methyl [benzoic]acid (BAY 58-2667) stabilized the enzyme, only the latter activated the NO-insensitive sGC variant. Importantly, in isolated cells, in blood vessels, and in vivo, BAY 58-2667 was more effective and potentiated under pathophysiological and oxidative stress conditions. This therapeutic principle preferentially dilates diseased versus normal blood vessels and may have far-reaching implications for the currently investigated clinical use of BAY 58-2667 as a unique diagnostic tool and highly innovative vascular therapy.
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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.