ArticleJournal of molecular and cellular cardiology2010
deltaPKC inhibition or varepsilonPKC activation repairs endothelial vascular dysfunction by regulating eNOS post-translational modification.
Article in Journal of molecular and cellular cardiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 47 citations in OpenAlex.
- Endothelial Piezo1 Hyperactivity Drives Neurovascular Dysfunction in Hypertension.Circulation research · 2026Article
- PKCδ regulates the vascular biology in diabetic atherosclerosis.Cell communication and signaling : CCS · 2023Review
- Nitric Oxide/Cyclic GMP-Dependent Calcium Signalling Mediates IL-6- and TNF-α-Induced Expression of Glial Fibrillary Acid Protein.Journal of molecular neuroscience : MN · 2021Article
- β-Cyclodextrin Inhibits Monocytic Adhesion to Endothelial Cells through Nitric Oxide-Mediated Depletion of Cell Adhesion Molecules.Molecules (Basel, Switzerland) · 2020Article
- Endothelial Aldehyde Dehydrogenase 2 as a Target to Maintain Vascular Wellness and Function in Ageing.Biomedicines · 2020Review
- Hydrogen Sulfide Protects Against Uremic Accelerated Atherosclerosis via nPKCδ/Akt Signal Pathway.Frontiers in molecular biosciences · 2020Article
- Far-infrared Ray-mediated Antioxidant Potentials are Important for Attenuating Psychotoxic Disorders.Current neuropharmacology · 2019Review
- Evolving mechanisms of vascular smooth muscle contraction highlight key targets in vascular disease.Biochemical pharmacology · 2018Review
- Aquaporin Membrane Channels in Oxidative Stress, Cell Signaling, and Aging: Recent Advances and Research Trends.Oxidative medicine and cellular longevity · 2018Review
- Flow signaling and atherosclerosis.Cellular and molecular life sciences : CMLS · 2017Review
- Protein Kinase C as Regulator of Vascular Smooth Muscle Function and Potential Target in Vascular Disorders.Advances in pharmacology (San Diego, Calif.) · 2017Review
- Regulation of pulmonary endothelial barrier function by kinases.American journal of physiology. Lung cellular and molecular physiology · 2016Review
- Targeting endothelial cell metabolism for cardio-protection from the toxicity of antitumor agents.Cardio-oncology (London, England) · 2016Review
- Monitoring Endothelial and Tissue Responses to Cobalt Ferrite Nanoparticles and Hybrid Hydrogels.PloS one · 2016Article
- PKCε-CREB-Nrf2 signalling induces HO-1 in the vascular endothelium and enhances resistance to inflammation and apoptosis.Cardiovascular research · 2015Article
- Characterization of zofenoprilat as an inducer of functional angiogenesis through increased H2 S availability.British journal of pharmacology · 2015Article
- Mitochondrial reactive oxygen species at the heart of the matter: new therapeutic approaches for cardiovascular diseases.Circulation research · 2015Review
- PKC and AKT Modulate cGMP/PKG Signaling Pathway on Platelet Aggregation in Experimental Sepsis.PloS one · 2015Article
- Protein kinase C delta modulates endothelial nitric oxide synthase after cardiac arrest.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2014Article
- Enhancement of interaction of BSEP and HAX-1 on the canalicular membrane of hepatocytes in a mouse model of cholesterol cholelithiasis.International journal of clinical and experimental pathology · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The balance between endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) and reactive oxygen species (ROS) production determines endothelial-mediated vascular homeostasis. Activation of protein kinase C (PKC) has been linked to imbalance of the eNOS/ROS system, which leads to endothelial dysfunction. We previously found that selective inhibition of delta PKC (deltaPKC) or selective activation of epsilon PKC (varepsilonPKC) reduces oxidative damage in the heart following myocardial infarction. In this study we determined the effect of these PKC isozymes in the survival of coronary endothelial cells (CVEC). We demonstrate here that serum deprivation of CVEC increased eNOS-mediated ROS levels, activated caspase-3, reduced Akt phosphorylation and cell number. Treatment with either the deltaPKC inhibitor, deltaV1-1, or the varepsilonPKC activator, psivarepsilonRACK, inhibited these effects, restoring cell survival through inhibition of eNOS activity. The decrease in eNOS activity coincided with specific de-phosphorylation of eNOS at Ser1179, and eNOS phosphorylation at Thr497 and Ser116. Furthermore, deltaV1-1 or psivarepsilonRACK induced physical association of eNOS with caveolin-1, an additional marker of eNOS inhibition, and restored Akt activation by inhibiting its nitration. Together our data demonstrate that (1) in endothelial dysfunction, ROS and reactive nitrogen species (RNS) formation result from uncontrolled eNOS activity mediated by activation of deltaPKC or inhibition of varepsilonPKC; (2) inhibition of deltaPKC or activation of varepsilonPKC corrects the perturbed phosphorylation state of eNOS, thus increasing cell survival. Since endothelial health ensures better tissue perfusion and oxygenation, treatment with a deltaPKC inhibitor and/or an varepsilonPKC activator in diseases of endothelial dysfunction should be considered.
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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.