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A Microphysiological System to Study Leukocyte-Endothelial Cell Interaction during Inflammation
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deltaPKC inhibition or varepsilonPKC activation repairs endothelial vascular dysfunction by regulating eNOS
Martina Monti1, Sandra Donnini, Antonio Giachetti
1Department of Molecular Biology, University of Siena, Via Aldo Moro, 2, 53100, Siena, Italy.
Journal of Molecular and Cellular Cardiology
|November 17, 2009
Summary
Selective inhibition of delta protein kinase C (PKC) or activation of epsilon PKC improves coronary endothelial cell survival by restoring the balance of nitric oxide synthase (eNOS) and reactive oxygen species (ROS). This targets endothelial dysfunction.
Area of Science:
- Cardiovascular Biology
- Cellular Signaling
- Endothelial Function
Background:
- Endothelial homeostasis relies on the balance between nitric oxide (NO) and reactive oxygen species (ROS).
- Protein kinase C (PKC) activation disrupts this balance, leading to endothelial dysfunction.
- Previous work showed deltaPKC inhibition and epsilonPKC activation protect the heart post-myocardial infarction.
Purpose of the Study:
- To investigate the role of deltaPKC and epsilonPKC isozymes in coronary endothelial cell (CVEC) survival.
- To determine if modulating these PKC isozymes affects eNOS activity and cell viability under stress.
Main Methods:
- Serum deprivation was used to induce stress in CVECs.
- The effects of deltaPKC inhibitor (deltaV1-1) and epsilonPKC activator (psivarepsilonRACK) were assessed.
- Key markers including eNOS activity, phosphorylation, Akt activation, caspase-3, and cell number were measured.
Main Results:
- Serum deprivation increased eNOS-mediated ROS, activated caspase-3, and reduced cell survival.
- Treatment with deltaV1-1 or psivarepsilonRACK restored cell survival by inhibiting eNOS activity.
- These treatments normalized eNOS phosphorylation, increased eNOS-caveolin-1 association, and restored Akt activation.
Conclusions:
- Uncontrolled eNOS activity, driven by deltaPKC activation or epsilonPKC inhibition, contributes to ROS/RNS formation in endothelial dysfunction.
- Inhibiting deltaPKC or activating epsilonPKC corrects eNOS phosphorylation, enhances cell survival, and offers a potential therapeutic strategy for endothelial dysfunction.
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