Hydrogen Sulfide (H2S) and the Cardiovascular System

Hydrogen sulfide (H2S) has relatively recently been added to a list of endogenously produced gaseous signalling molecules. Our understanding of the science of H2S has advanced rapidly in recent years as exemplified by the fact that, within a mere 10 years, a range of H2S releasing drugs have already been synthesisied and some indeed are entering clinical trials. However, the precise biological roles of endogenous H2S are not fully understood. In this respect, slow releasing H2S donors, such as GYY4137, have played a part in elucidating the complex roles of this gas in the body and are also beginning to show promise as possible therapeutics in inflammation - an area in which the function of H2S remains ambiguous. -- This thesis attempts to provide some additional clarity to the biological significance of endogenous H2S. The first part of this work examines the release of endothelial cell derived H2S in vitro and the consequences of deleting the genetic encoding of nitric oxide synthase on tissue H2S biosynthesis in mice. As part of this study, I show that the methods currently utilised to measure H2S are insufficiently sensitive/reliable to convincingly demonstrate the release of H2S from cells in vitro. In addition, data reported herein has demonstrated that knocking out endothelial cell nitric oxide synthase (eNOS) results in an increase in tissue H2S synthesising activity, which is hypothesised to be a compensatory mechanism as a result of the loss of NOS. -- The second part of this thesis examines the role of H2S in inflammation and provides further evidence for its anti-inflammatory activity both in vitro and in vivo. In addition, this thesis has shown the ’added benefit’ of slow-releasing H2S donors (c.f. conventional sulfide salt based donors) in that the H2S released from slow-releasing donors is progressive and does not instantaneously expose cells to potentially cytotoxic amounts of H2S.

Name dc:type.qualificationname

Doctor of Philosophy

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

King's College London

Year dc:date.issued

2012

Author dc:creator

• Hsu, Anna

Advisors dc:contributor.advisor

• Nandi, Manasi
• Pearson, Jeremy David
• Moore, Philip Keith

Language dc:language

eng

Identifier

oai:kclpure.kcl.ac.uk:studenttheses/c1361731-0831-46f6-803a-c276ee71a4d6

OAI identifier oai:identifier

oai:kclpure.kcl.ac.uk:studenttheses/c1361731-0831-46f6-803a-c276ee71a4d6