Abstract
Abstract 120: Methamphetamine-induced Cardiomyopathy Associated With Mitochondrial Dysfunction, Cardiac Fibrosis and Hypertrophy
Circulation research, Vol.125(Suppl_1)
08/02/2019
DOI: 10.1161/res.125.suppl_1.120
Abstract
Introduction:
Methamphetamine (METH) is one of the most commonly abused illicit drugs in the United States, exerting a range of adverse effects upon multiple organ systems. Cardiovascular complications are among the major causes of death in METH users. METH-induced cardiomyopathy is a poorly characterized disease entity as METH-induced molecular perturbations, and histopathological changes in the heart remain under-explored.
Objectives:
We studied histopathology in the hearts of human METH users. We also observed the histological alteration and changes in mitochondrial function in mice that received ‘binge’ administration of METH.
Methods and Results:
We obtained 32 autopsy heart samples from humans with positive toxicology for chronic METH use and performed Sirius Red and Masson’s Trichrome (MT) staining on left ventricular (LV) sections. Notably, chronic METH user hearts showed intense perivascular and interstitial fibrosis in LVs. ‘Binge’ METH administration in mice for 4 weeks showed an increase in heart weight-to-tibia length and increase in myocyte cross-sectional area in WGA stained LVs compared to saline-treated mice. Sirius red and MT staining also showed an increase in perivascular and interstitial fibrosis in METH mice heart. Isolated mitochondria from METH-treated mice heart showed suppressed mitochondrial bioenergetics measured by Seahorse Analyzer. Immunoblotting in heart lysates and mitochondrial fractions showed altered mitochondrial dynamics regulatory proteins expression in METH mice compared to control saline group. METH-treated cultured neonatal rat ventricular cardiomyocytes also showed suppression of mitochondrial respiration and mitochondrial network disorganization indicating a direct effect of METH on cardiomyocytes.
Conclusions:
We report that maladaptive cardiac fibrotic remodeling is typical in a human and pre-clinical mouse model of METH abuse. ‘Binge’ METH exposure in mice induces cardiac hypertrophy, cardiac fibrosis, and suppression of mitochondrial respiration. Thus, chronic METH use induces maladaptive cardiac remodeling associated with mitochondrial dysfunction.
Details
- Title: Subtitle
- Abstract 120: Methamphetamine-induced Cardiomyopathy Associated With Mitochondrial Dysfunction, Cardiac Fibrosis and Hypertrophy
- Creators
- Chowdhury S Abdullah - Louisiana State University Health Sciences Center ShreveportRicha Aishwarya - Louisiana State University Health Sciences Center ShreveportShafiul Alam - Louisiana State University Health Sciences Center ShreveportMahboob Morshed - Louisiana State University Health Sciences Center ShreveportGopi K Kolluru - Louisiana State University Health Sciences Center ShreveportJames Traylor - Louisiana State University Health Sciences Center ShreveportSumitra Miriyala - Louisiana State University Health Sciences Center ShreveportManikandan Panchatcharam - Louisiana State University Health Sciences Center ShreveportMatthew D Woolard - Louisiana State University Health Sciences Center ShreveportNicholas E Goeders - Louisiana State University Health Sciences Center ShreveportXioa-Hong Lu - Louisiana State University Health Sciences Center ShreveportPaari S Dominic - Louisiana State University Health Sciences Center ShreveportChristopher G Kevil - Louisiana State University Health Sciences Center ShreveportA. Wayne Orr - Louisiana State University Health Sciences Center ShreveportNorman R Harris - Louisiana State University Health Sciences Center ShreveportFelicity N. E Gavins - Louisiana State University Health Sciences Center ShreveportMd. Shenuarin Bhuiyan - Louisiana State University Health Sciences Center Shreveport
- Resource Type
- Abstract
- Publication Details
- Circulation research, Vol.125(Suppl_1)
- DOI
- 10.1161/res.125.suppl_1.120
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 08/02/2019
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984367242602771
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