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Circulating humanin levels are associated with preserved coronary endothelial function


Widmer, R J; Flammer, A J; Herrmann, J; Rodriguez-Porcel, M; Wan, J; Cohen, P; Lerman, L O; Lerman, A (2013). Circulating humanin levels are associated with preserved coronary endothelial function. American Journal of Physiology - Heart and Circulatory Physiology, 304(3):H393-H397.

Abstract

Humanin is a small endogenous antiapoptotic peptide, originally identified as protective against Alzheimer's disease, but subsequently also found on human endothelium as well as carotid artery plaques. Endothelial dysfunction is a precursor to the development of atherosclerotic plaques, which are characterized by a highly proinflammatory, reactive oxygen species, and apoptotic milieu. Previous animal studies demonstrated that humanin administration may improve endothelial function. Thus the aim of this study was to test the hypothesis that patients with coronary endothelial dysfunction have reduced systemic levels of humanin. Forty patients undergoing coronary angiography and endothelial function testing were included and subsequently divided into two groups based on coronary blood flow (CBF) response to intracoronary acetylcholine (normal >/= 50% increase from baseline, n = 20 each). Aortic plasma samples were obtained at the time of catheterization for the analysis of humanin levels and traditional biomarkers of atherosclerosis including C-reactive protein, Lp-Pla(2), and homocysteine. Baseline characteristics were similar in both groups. Patients with coronary endothelial dysfunction (change in CBF = -33 +/- 25%) had significantly lower humanin levels (1.3 +/- 1.1 vs. 2.2 +/- 1.5 ng/ml, P = 0.03) compared with those with normal coronary endothelial function (change in CBF = 194 +/- 157%). There was a significant and positive correlation between improved CBF and humanin levels (P = 0.0091) not seen with changes in coronary flow reserve (P = 0.76). C-reactive protein, Lp-Pla(2), and homocysteine were not associated with humanin levels. Thus we observed that preserved human coronary endothelial function is uniquely associated with higher systemic humanin levels, introducing a potential diagnostic and/or therapeutic target for patients with coronary endothelial function.

Abstract

Humanin is a small endogenous antiapoptotic peptide, originally identified as protective against Alzheimer's disease, but subsequently also found on human endothelium as well as carotid artery plaques. Endothelial dysfunction is a precursor to the development of atherosclerotic plaques, which are characterized by a highly proinflammatory, reactive oxygen species, and apoptotic milieu. Previous animal studies demonstrated that humanin administration may improve endothelial function. Thus the aim of this study was to test the hypothesis that patients with coronary endothelial dysfunction have reduced systemic levels of humanin. Forty patients undergoing coronary angiography and endothelial function testing were included and subsequently divided into two groups based on coronary blood flow (CBF) response to intracoronary acetylcholine (normal >/= 50% increase from baseline, n = 20 each). Aortic plasma samples were obtained at the time of catheterization for the analysis of humanin levels and traditional biomarkers of atherosclerosis including C-reactive protein, Lp-Pla(2), and homocysteine. Baseline characteristics were similar in both groups. Patients with coronary endothelial dysfunction (change in CBF = -33 +/- 25%) had significantly lower humanin levels (1.3 +/- 1.1 vs. 2.2 +/- 1.5 ng/ml, P = 0.03) compared with those with normal coronary endothelial function (change in CBF = 194 +/- 157%). There was a significant and positive correlation between improved CBF and humanin levels (P = 0.0091) not seen with changes in coronary flow reserve (P = 0.76). C-reactive protein, Lp-Pla(2), and homocysteine were not associated with humanin levels. Thus we observed that preserved human coronary endothelial function is uniquely associated with higher systemic humanin levels, introducing a potential diagnostic and/or therapeutic target for patients with coronary endothelial function.

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18 citations in Web of Science®
17 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Acetylcholine/diagnostic use Adult Atherosclerosis/blood/physiopathology Biological Markers Blood Chemical Analysis Coronary Angiography Coronary Circulation/physiology Coronary Disease/*physiopathology Coronary Vessels/*physiology/physiopathology Diabetes Mellitus, Type 2/blood Endothelium, Vascular/*physiology Female Heart Failure/physiopathology Hemodynamics/physiology Humans Hypertension/blood Intracellular Signaling Peptides and Proteins/*metabolism/*physiology Lipids/blood Male Microcirculation/physiology Middle Aged Vasodilator Agents/diagnostic use
Language:English
Date:2013
Deposited On:01 Nov 2013 08:33
Last Modified:05 Apr 2016 17:05
Publisher:American Physiological Society
ISSN:0363-6135
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1152/ajpheart.00765.2012
PubMed ID:23220334

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