Hydrogen sulfide (H2S) is an important signaling molecule with potent cytoprotective actions in cardiovascular systems. Current results indicate that modulation of H2S levels could have potential therapeutic value for a number of disease states such as vasodilation, anti-inflammation, and anti-oxidation. However, the exact mechanisms of action are still unclear and the actual H2S concentration/flux needed to exhibit the optimal protection in those disease models are to be determined. This lack of knowledge presents a major burden in the development of H2S based therapy. To solve this problem, research tools that can effectively detect H2S and specifically supply/remove H2S in biological samples are needed. In this application we plan to develop highly sensitive fluorescent probes for H2S detection. We will also develop novel H2S releasing agents and scavenging agents. The new chemicals will be used to determine the optimal H2S profiles for cardioprotection in models of myocardial ischemia/reperfusion (MI/R) injury and heart failure. This study will establish useful protocols guiding the development of H2S therapy.

Public Health Relevance

The fields of hydrogen sulfide (H2S) physiology and pharmacology have been rapidly growing in recent years, but a number of fundamental issues must be addressed to advance our understanding of the biology and clinical potential of H2S in the future. In this project, we plan to develop highly sensitive fluorescent sensors for the detection of H2S, highly specific donors to supply H2S and effective scavengers to remove H2S under pathological conditions. These novel chemicals will be used to understand the effects of H2S in cardioprotection. We expect these studies will have great impact on the development of H2S-based therapy for heart diseases.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL151398-01
Application #
9940566
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Wong, Renee P
Project Start
2020-05-11
Project End
2024-04-30
Budget Start
2020-05-11
Budget End
2021-04-30
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Brown University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912