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.