Journal article
Methamphetamine causes cardiovascular dysfunction via cystathionine gamma lyase and hydrogen sulfide depletion
Redox biology, Vol.57, pp.102480-102480
11/2022
DOI: 10.1016/j.redox.2022.102480
PMCID: PMC9513700
PMID: 36167027
Abstract
Methamphetamine (METH) is an addictive illicit drug used worldwide that causes significant damage to blood vessels resulting in cardiovascular dysfunction. Recent studies highlight increased prevalence of cardiovascular disease (CVD) and associated complications including hypertension, vasospasm, left ventricular hypertrophy, and coronary artery disease in younger populations due to METH use. Here we report that METH administration in a mouse model of ‘binge and crash’ decreases cardiovascular function via cystathionine gamma lyase (CSE), hydrogen sulfide (H2S), nitric oxide (NO) (CSE/H2S/NO) dependent pathway. METH significantly reduced H2S and NO bioavailability in plasma and skeletal muscle tissues co-incident with a significant reduction in flow-mediated vasodilation (FMD) and blood flow velocity revealing endothelial dysfunction. METH administration also reduced cardiac ejection fraction (EF) and fractional shortening (FS) associated with increased tissue and perivascular fibrosis. Importantly, METH treatment selectively decreased CSE expression and sulfide bioavailability along with reduced eNOS phosphorylation and NO levels. Exogenous sulfide therapy or endothelial CSE transgenic overexpression corrected cardiovascular and associated pathological responses due to METH implicating a central molecular regulatory pathway for tissue pathology. These findings reveal that therapeutic intervention targeting CSE/H2S bioavailability may be useful in attenuating METH mediated cardiovascular disease.
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Details
- Title: Subtitle
- Methamphetamine causes cardiovascular dysfunction via cystathionine gamma lyase and hydrogen sulfide depletion
- Creators
- Gopi K. Kolluru - Louisiana State University Health Sciences Center ShreveportJohn D. Glawe - Department of Pathology, LSU Health Sciences Center- Shreveport, USASibile Pardue - Department of Pathology, LSU Health Sciences Center- Shreveport, USAAhmad Kasabali - Department of Pathology, LSU Health Sciences Center- Shreveport, USAShafiul Alam - Department of Pathology, LSU Health Sciences Center- Shreveport, USASaranya Rajendran - Indiana University BloomingtonAllison L. Cannon - Department of Pathology, LSU Health Sciences Center- Shreveport, USAChowdhury S. Abdullah - Department of Pathology, LSU Health Sciences Center- Shreveport, USAJames G. Traylor - Department of Pathology, LSU Health Sciences Center- Shreveport, USARodney E. Shackelford - Department of Pathology, LSU Health Sciences Center- Shreveport, USAMatthew D. Woolard - Department of Microbiology and Immunology, LSU Health Sciences Center- Shreveport, USAA. Wayne Orr - Department of Pathology, LSU Health Sciences Center- Shreveport, USANicholas E. Goeders - Department of Pharmacology, Toxicology & Neuroscience, LSU Health Sciences Center- Shreveport, USAPaari Dominic - Division of Cardiology Department of Medicine, LSU Health Sciences Center- Shreveport, USAMd Shenuarin S. Bhuiyan - Department of Pathology, LSU Health Sciences Center- Shreveport, USAChristopher G. Kevil - Department of Pathology, LSU Health Sciences Center- Shreveport, USA
- Resource Type
- Journal article
- Publication Details
- Redox biology, Vol.57, pp.102480-102480
- DOI
- 10.1016/j.redox.2022.102480
- PMID
- 36167027
- PMCID
- PMC9513700
- NLM abbreviation
- Redox Biol
- ISSN
- 2213-2317
- eISSN
- 2213-2317
- Publisher
- Elsevier B.V
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: P20GM121307, HL098435, HL122354, HL131844, HL133497, HL141155, HL145753, HL149264; DOI: 10.13039/100000057, name: National Institute of General Medical Sciences
- Language
- English
- Date published
- 11/2022
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984367121302771
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