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Pivotal role of hydrogen sulphide in reversal of impaired platelet nitric oxide signaling in coronary artery spasm
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  • Mdhasan Imam,
  • Thanh Nguyen,
  • Irene Stafford,
  • Saifei Liu,
  • Tamila Heresztyn,
  • Yuliy Chirkov,
  • John Horowitz
Mdhasan Imam
The University of Adelaide

Corresponding Author:[email protected]

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Thanh Nguyen
The University of Adelaide
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Irene Stafford
The University of Adelaide
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Saifei Liu
The University of Adelaide
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Tamila Heresztyn
The University of Adelaide
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Yuliy Chirkov
The University of Adelaide
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John Horowitz
The University of Adelaide
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Background and purpose: The pathophysiology of coronary artery spasm ( CAS), with its associated ischaemic crises, is currently poorly understood, and treatment is frequently ineffective. In view of increasing evidence that platelet- platelet based defects may occur in CAS patients,. we investigated platelet reactivity in CAS patients and whether symptomatic crises reflect activation of platelet-endothelial interactions. Experimental approach: CAS patients were evaluated during acute and/or chronic symptomatic phases, and compared with healthy control subjects. Inhibition of platelet aggregation with ADP by the nitric oxide (NO) donor sodium nitroprusside (SNP), . and plasma levels of syndecan-1 (glycocalyx shedding marker), tryptase (mast cell activation marker), and platelet microparticles were measured. Key Results: Inhibition of aggregation by SNP was impaired in chronic CAS, and tended to deteriorate further during symptomatic crises, while plasma levels of syndecan-1, tryptase and platelet microparticles increased. Infusion of high dose N-acetylcysteine (NAC) plus glyceryl trinitrate rapidly restored platelet responsiveness to SNP and decreased plasma syndecan-1 levels. The effect of NAC on platelet responsiveness to SNP was mimicked in vitro by the H2S donor NaHS. Conversely, inhibition of enzymatic release of H2S attenuated NAC effect. Conclusion and Implications: CAS is associated with substantial impairment of platelet NO signaling. During acute symptomatic exacerbations, platelet resistance to NO is aggravated, together with mast cell activation and damage to both vasculature and platelets. NAC reverses platelet resistance to NO via release of H2S, and reverses glycocalyx shedding during symptomatic crises: this suggests that H2S donors may correct the pathophysiological anomalies underlying CAS.
31 Mar 2020Submitted to British Journal of Pharmacology
01 Apr 2020Submission Checks Completed
01 Apr 2020Assigned to Editor
15 Apr 2020Reviewer(s) Assigned
21 Jun 2020Review(s) Completed, Editorial Evaluation Pending
26 Jun 2020Editorial Decision: Revise Minor
03 Sep 20201st Revision Received
06 Sep 2020Assigned to Editor
06 Sep 2020Submission Checks Completed
09 Sep 2020Reviewer(s) Assigned
29 Sep 2020Review(s) Completed, Editorial Evaluation Pending
30 Oct 2020Editorial Decision: Revise Minor
04 Dec 20202nd Revision Received
06 Dec 2020Submission Checks Completed
06 Dec 2020Assigned to Editor
06 Dec 2020Review(s) Completed, Editorial Evaluation Pending
18 Dec 2020Editorial Decision: Revise Minor
23 Dec 20203rd Revision Received
24 Dec 2020Submission Checks Completed
24 Dec 2020Assigned to Editor
26 Dec 2020Review(s) Completed, Editorial Evaluation Pending
04 Jan 2021Editorial Decision: Accept