Abstract
Abstract 421: Norepinephrine Catabolism Drives Cardiac Fibroblast Activation via Monoamine Oxidase Activity and Rage/β-adrenergic Signaling
Circulation research, Vol.127(Suppl_1)
07/31/2020
DOI: 10.1161/res.127.suppl_1.421
Abstract
The mitochondrial enzyme monoamine oxidase A (MAO-A) plays an increasingly appreciated role in cardiac remodeling induced by diabetes and ischemic injury. Oxidative deamination of norepinephrine (NE) by MAO-A generates 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL) and H
2
O
2
. Isolation and quantification of catechol-modified proteins from cardiac fibroblast lysate using an aminophenylboronic acid resin showed an MAO-dependent accumulation of catechol adducts in NE-treated cells (P<0.05). Our lab has previously observed increased expression and activity of MAO in myocardium of diabetes patients compared with age-matched nondiabetic patients. Moreover, preliminary data suggest that catecholaldehydes and other biogenic aldehydes might contribute to the pathogenesis of cardiac fibrosis in diabetic cardiomyopathy via pro-fibrotic signaling mechanisms. We hypothesize that NE activates fibroblasts by both canonical pathways (i.e, adrenergic receptors) and by monoamine oxidase-mediated catabolism and activation of the receptor for advanced glycation endproducts (RAGE). Treatment of cardiac fibroblasts with NE (1 μM) resulted in accelerated proliferation, enhanced collagen I & III secretion, robust increases in mitochondrial and total cellular ROS, and upregulated pro-fibrotic gene expression. These effects were abrogated by co-administration of RAGE antagonist FPS-ZM1, MAO inhibitors, β-blocker propranolol, and the aldehyde scavenger carnosine (P<0.05). These findings suggest that NE (and other catecholamines) may influence extracellular matrix remodeling via multiple pathways, including adrenergic and also RAGE, via MAO-mediated catabolism.
Details
- Title: Subtitle
- Abstract 421: Norepinephrine Catabolism Drives Cardiac Fibroblast Activation via Monoamine Oxidase Activity and Rage/β-adrenergic Signaling
- Creators
- Blake Monroe - University of IowaEthan J Anderson - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Circulation research, Vol.127(Suppl_1)
- DOI
- 10.1161/res.127.suppl_1.421
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 07/31/2020
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Health and Human Physiology; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984366311602771
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