Abstract
Abstract 12954: A Genotype-Phenotype Link Between Cardiac Monoamine Oxidase Activity and Arrhythmogenic Potential Using a Translational Approach
Circulation (New York, N.Y.), Vol.144(Suppl_1), p.A12954
11/16/2021
DOI: 10.1161/circ.144.suppl_1.12954
Abstract
Introduction:
Monoamine oxidase (MAO) has emerged as an intriguing drug target for heart disease because of the toxicity of the oxidative catechol metabolites produced. Our group has recently shown that a high rate of MAO activity in atrial myocardium is associated with a greater incidence of postoperative atrial fibrillation (POAF) following coronary artery bypass graft surgery (CABG).
Hypothesis:
Cardiac MAO deficiency lowers arrhythmogenic potential.
Methods and Results:
In a cohort of age-matched CABG patients (N=288, 26% female, 20% African-American), we performed DNA-sequencing analysis of
maoA,B
while assessing maximal MAO-A and -B enzyme activity with norepinephrine (NE) in fresh atrial tissue from a subset (N=110) of these patients. Patients homozygous for
maoA
synonymous variant rs1800464, and
maoB
intron variant rs5905512, had lower NE-supported MAO activity (
Figure 1
, 0 = ref, 1=het, 2=homoz) and lower incidence of POAF (OR 0.6 ± 0.1 and 0.9 ± 0.02, respectively). Mice with cardiomyocyte-specific MAO-A deficiency (cMAOA
-/-
) had 2-fold lower rates of epinephrine/caffeine-induced ventricular tachycardia (VT) compared with wild-type (
Figure 2
, *P<0.05). Moreover, cardiomyocytes from cMAOA
-/-
mice had increased fractional shortening, faster relaxation and shorter Ca
2+
transient duration (P<0.05). Alterations in Ca
2+
handling in the cMAOA
-/-
mice were accompanied by decreased epinephrine-induced phosphorylation of CamKII and ryanodine receptor (P<0.05).
Conclusions:
Collectively, these findings suggest that decreasing MAO activity lowers arrhythmogenic potential in the heart, and that cardiac MAO may be a therapeutic target for POAF.
Details
- Title: Subtitle
- Abstract 12954: A Genotype-Phenotype Link Between Cardiac Monoamine Oxidase Activity and Arrhythmogenic Potential Using a Translational Approach
- Creators
- Qian Shi - University of IowaAlexander Hart - UIowa- College of Pharmacy, Iowa City, IAAndrew Jatis - UIowa- College of Pharmacy, Iowa City, IANathan Karlan - UIowa- College of Pharmacy, Iowa City, IAShahab Akhter - East Carolina UniversityJean C ShihRyan M Smith - UIowa- College of Pharmacy, Iowa City, IALong-sheng Song - University of IowaEthan J Anderson - UIowa- College of Pharmacy, Iowa City, IA
- Resource Type
- Abstract
- Publication Details
- Circulation (New York, N.Y.), Vol.144(Suppl_1), p.A12954
- DOI
- 10.1161/circ.144.suppl_1.12954
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Language
- English
- Date published
- 11/16/2021
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Health and Human Physiology; Internal Medicine; Biochemistry and Molecular Biology; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984297353102771
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