CSE regulation of vascular remodeling

CSE对血管重塑的调节

• 批准号: 10630127
• 负责人: Christopher G Kevil
• 金额: $ 42.8万
• 依托单位: LOUISIANA STATE UNIV HSC SHREVEPORT
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10630127
• 关键词: Affect; American; Analytical Chemistry; Area; Binding; Biochemical Pathway; Biological Availability; Biology; Blood Vessels; Blood flow; Brain Hypoxia-Ischemia; Cardiovascular Diseases; Cardiovascular Physiology; Cells; Cellular biology; Chemicals; Chronic; Clinical; Cystathionine; Cysteine Desulfhydrase; Data; Disease; Endothelial Cells; Endothelium; Enzymes; Experimental Models; FDA approved; Generations; Glutathione Disulfide; Growth; Health; Hydrogen Sulfide; Hypoxia; Immune; In Vitro; Ischemia; Laboratories; Limb structure; Lyase; Macrophage; Macrophage Activation; Measurement; Mediator; Metabolism; Methods; Modality; Modeling; Molecular; Molecular Target; Mus; Nitric Oxide; Organ; Participant; Pathway interactions; Peripheral; Peripheral Vascular Diseases; Peripheral arterial disease; Permeability; Play; Population; Post-Translational Protein Processing; Post-Translational Regulation; Prevalence; Prevention; Production; Proliferating; Proteins; Regulation; Research; Risk Factors; Role; Signal Transduction; Specimen; Sulfides; Sulfur; Testing; Therapeutic; Tissues; Vascular Diseases; Vascular remodeling; Vascularization; angiogenesis; cardiovascular health; cell growth regulation; cofactor; critical limb Ischemia; cytokine; improved; insight; monocyte; mutant mouse model; novel; persulfides; polysulfide; recruit; response; therapeutically effective; tool

Project Summary Hydrogen sulfide synthesis and metabolism is an important participant in cardiovascular health and function. Specifically, our laboratory has shown that cystathionine g-lyase (CSE) expression and function play a critical role in ischemic vascular remodeling responses of arteriogenesis and angiogenesis. Moreover, our group has revealed important chemical biology and pathophysiological relationships between sulfide and nitric oxide metabolites in clinical vascular disease conditions, which may be important for cooperative regulation of ischemic vascular remodeling. However, numerous molecular and cellular mechanisms remain completely unknown in these responses including: the role of specific cell populations in producing discrete sulfide species during ischemic vascular remodeling, how different sulfide metabolites modulate nitric oxide (NO) bioavailability through various biochemical pathways, and mechanisms regulating rapid increases in CSE activity dependent sulfide metabolite bioavailability during hypoxia. This application will address these important unknown areas using novel tissue specific CSE mutant mouse models, cutting edge analytical chemistry measurement methods of sulfide and NO species, cellular and molecular methods to discover posttranslational regulation of CSE protein activity in response to hypoxia, and clinical tissue specimens to better understand persulfide and polysulfide during vascular remodeling and disease. Using the models and tools above, this proposal will examine the hypothesis that endothelial cell and monocyte CSE dependent polysulfide formation differentially regulates ischemic vascular remodeling and NO bioavailability. Three specific aims will be pursued to test the hypothesis including: 1) determine the mechanisms of endothelial CSE regulation of ischemic vascular remodeling and how it controls vascular cell NO bioavailability, 2) determine the mechanisms of monocyte CSE regulation of arteriogenesis, and 3) determine mechanisms of CSE activity and expression in experimental models and clinical specimens. Completion of this project will provide crucial new basic insight that is not currently available regarding mechanisms of CSE regulation and polysulfide effects on cell biology during ischemic vascular remodeling.

项目总结

项目成果

Bad Smells and Broken DNA: A Tale of Sulfur-Nucleic Acid Cooperation.

• DOI: 10.3390/antiox10111820
• 发表时间: 2021-11-17
• 期刊: Antioxidants (Basel, Switzerland)
• 作者: Shackelford RE;Li Y;Ghali GE;Kevil CG
• 通讯作者: Kevil CG

Plasma hydrogen sulfide: A biomarker of Alzheimer's disease and related dementias.

• DOI: 10.1002/alz.12305
• 发表时间: 2021-08
• 期刊: Alzheimer's & dementia : the journal of the Alzheimer's Association
• 作者: Disbrow E;Stokes KY;Ledbetter C;Patterson J;Kelley R;Pardue S;Reekes T;Larmeu L;Batra V;Yuan S;Cvek U;Trutschl M;Kilgore P;Alexander JS;Kevil CG
• 通讯作者: Kevil CG

Ethylmalonic Encephalopathy 1 Protein Is Increased in Colorectal Adenocarcinoma.

• DOI: 10.21873/anticanres.15286
• 发表时间: 2021-10
• 期刊: Anticancer research
• 影响因子: 2
• 作者: Ozluk E;Coppola D;Mohammad IZ;Islam T;Ghali G;Kevil CG;Shackelford RE
• 通讯作者: Shackelford RE

Molecular Functions of Hydrogen Sulfide in Cancer.

硫化氢在癌症中的分子功能。

• DOI: 10.3390/pathophysiology28030028
• 发表时间: 2021-09-20
• 期刊: Pathophysiology : the official journal of the International Society for Pathophysiology
• 作者: Shackelford RE;Mohammad IZ;Meram AT;Kim D;Alotaibi F;Patel S;Ghali GE;Kevil CG
• 通讯作者: Kevil CG

Mitochondrial dysfunction and autophagy activation are associated with cardiomyopathy developed by extended methamphetamine self-administration in rats.

• DOI: 10.1016/j.redox.2022.102523
• 发表时间: 2022-12
• 期刊: REDOX BIOLOGY
• 影响因子: 11.4
• 作者: Abdullah, Chowdhury S.;Remex, Naznin Sultana;Aishwarya, Richa;Nitu, Sadia;Kolluru, Gopi K.;Traylor, James;Hartman, Brandon;King, Judy;Bhuiyan, Mohammad Alfrad Nobel;Hall, Nicole;Murnane, Kevin Sean;Goeders, Nicholas E.;Kevil, Christopher G.;Orr, A. Wayne;Bhuiyan, Md. Shenuarin
• 通讯作者: Bhuiyan, Md. Shenuarin