Next Article in Journal
Long-Term Changes in Cognition and Physiology after Low-Dose 16O Irradiation
Next Article in Special Issue
Sevoflurane, Propofol and Carvedilol Block Myocardial Protection by Limb Remote Ischemic Preconditioning
Previous Article in Journal
High Expression of IL-1RI and EP2 Receptors in the IL-1β/COX-2 Pathway, and a New Alternative to Non-Steroidal Drugs—Osthole in Inhibition COX-2
Previous Article in Special Issue
Beyond a Measure of Liver Function—Bilirubin Acts as a Potential Cardiovascular Protector in Chronic Kidney Disease Patients
Open AccessReview

New Therapeutic Implications of Endothelial Nitric Oxide Synthase (eNOS) Function/Dysfunction in Cardiovascular Disease

1
Center for Cardiology, Cardiology I—Laboratory of Molecular Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany
2
German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, 55131 Mainz, Germany
3
Department of Pharmacology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(1), 187; https://doi.org/10.3390/ijms20010187
Received: 2 December 2018 / Revised: 27 December 2018 / Accepted: 28 December 2018 / Published: 7 January 2019
The Global Burden of Disease Study identified cardiovascular risk factors as leading causes of global deaths and life years lost. Endothelial dysfunction represents a pathomechanism that is associated with most of these risk factors and stressors, and represents an early (subclinical) marker/predictor of atherosclerosis. Oxidative stress is a trigger of endothelial dysfunction and it is a hall-mark of cardiovascular diseases and of the risk factors/stressors that are responsible for their initiation. Endothelial function is largely based on endothelial nitric oxide synthase (eNOS) function and activity. Likewise, oxidative stress can lead to the loss of eNOS activity or even “uncoupling” of the enzyme by adverse regulation of well-defined “redox switches” in eNOS itself or up-/down-stream signaling molecules. Of note, not only eNOS function and activity in the endothelium are essential for vascular integrity and homeostasis, but also eNOS in perivascular adipose tissue plays an important role for these processes. Accordingly, eNOS protein represents an attractive therapeutic target that, so far, was not pharmacologically exploited. With our present work, we want to provide an overview on recent advances and future therapeutic strategies that could be used to target eNOS activity and function in cardiovascular (and other) diseases, including life style changes and epigenetic modulations. We highlight the redox-regulatory mechanisms in eNOS function and up- and down-stream signaling pathways (e.g., tetrahydrobiopterin metabolism and soluble guanylyl cyclase/cGMP pathway) and their potential pharmacological exploitation. View Full-Text
Keywords: cardiovascular disease; environmental stressors; life style/behavioral health risk factors; endothelial dysfunction; eNOS uncoupling; oxidative stress; inflammation cardiovascular disease; environmental stressors; life style/behavioral health risk factors; endothelial dysfunction; eNOS uncoupling; oxidative stress; inflammation
Show Figures

Figure 1

MDPI and ACS Style

Daiber, A.; Xia, N.; Steven, S.; Oelze, M.; Hanf, A.; Kröller-Schön, S.; Münzel, T.; Li, H. New Therapeutic Implications of Endothelial Nitric Oxide Synthase (eNOS) Function/Dysfunction in Cardiovascular Disease. Int. J. Mol. Sci. 2019, 20, 187.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop