Horn 2018 Eur Heart J
|Horn P, Haschemi J, Scheiber D, Szendroedi J, Zweck E, Sun R, Luppa PB, Saeed D, Boeken U, Kelm M, Roden M, Boege F, Westenfeld R (2018) Sympathomimetic beta-1AR autoantibodies in patients after heart transplantation are associated with higher mitochondrial coupling efficiency. Eur Heart J.|
Event: Eur Heart J
Sympathomimetic autoantibodies against the β1-adrenergic receptor (β1AR) are associated with chronic heart failure (CHF). Up to now, the mechanism involved in the pathogenic action of the autoantibodies on human myocardium remains unclear. Chronically elevated circulating catecholamines are observed in patients with CHF and are linked with mitochondrial dysfunction.
We aimed to study putative effects of circulating β1AR autoantibodies on myocardial mitochondrial function in patients with CHF undergoing heart transplantation (HTX).
In this prospective study we included 47 HTX patients, eight of which were included before HTX and monitored before and after transplantation. 119 patients with CHF NOT undergoing HTX served as control. β1AR autoantibodies were quantified via IgG binding to isolated, reconstituted, native human β1AR. Endomyocardial biopsies (EMB) were subjected to standard grading and additionally evaluated by quantitative immunohistochemistry of lymphocyte subtypes (CD3, LFA-1, CD45R0), adhesion molecules (ICAM-1), macrophages (Mac-1) and cytotoxic cells (perforin). Myocardial mitochondrial function was assessed ex vivo by high-resolution respirometry (Oroboros , Bioblast, Austria).
Prior to HTX, 23 of the heart transplant patients suffered from dilated cardiomyopathy (DCM), 22 suffered from ischemic cardiomyopathy (ICM) and two patients suffered from other forms of cardiomyopathy. Of the CHF patients, 69 exhibited DCM, 41 exhibited ICM and 9 patients exhibited other forms of cardiomyopathy.
HTX patients had significant lower levels of β1AR-autoantibodies than patients with CHF (161±27 ng/ml vs. 274±25 ng/ml, p=0.01), while mean values in both groups were well below the cut-off of the assay (500 ng/mL at the 2s limit). In patients undergoing HTX during the study period levels of β1A-autoantibodies decreased following HTX (249±173 ng/ml before vs. 93±72 ng/ml after HTX, p=0.03). Though well below the cut-off of the assay, β1AR-autoantibody values in HTX patients were quantitatively correlated with mitochondrial coupling efficacy and respiratory control ratio (RCR [State III mixed/LEAK], n=23, r=0.528, p=0.01). These patients did not exhibit similar correlations between β1AR-autoantibody levels and oxygen-flux in State III, fatty acids (r=-0.139, p=0.482) or oxidative phosphorylation capacity (r=0.065, p=0.741). Likewise, we did not observe any correlation between β1AR-autoantibodies and inflammatory cells in the myocardium.
We observed that β1AR autoantibody levels decreased post HTX. We surmise this phenomenon is due to immunosuppressive therapy and/or improvement of ejection fraction. Most notably, decreased β1AR autoantibody levels following HTX, where quantitatively correlated with more efficient O2 utilization by myocardial mitochondria, which might indicate a compensatory role of the autoantibodies in the failing myocardium.
Labels: MiParea: Respiration Pathology: Cardiovascular, Myopathy
Organism: Human Tissue;cell: Heart
Horn P(1), Haschemi J(1), Scheiber D(1), Szendroedi J(2), Zweck E(1), Sun R(3), Luppa PB(3), Saeed D(4), Boeken U(4), Kelm M(1), Roden M(2), Boege F(5), Westenfeld R(1)
- Dept Cardiology, Pneumology Angiology
- Inst Clinical Diabetology, German Diabetes Center, Leibniz Center Diabetes Research; Düsseldorf, Germany
- Dept Clinical Chemistry, Klinikum rechts der Isar, Technical Univ Munich, Germany
- Heinrich Heine Univ, Cardiovascular Surgery
- Inst Clinical Chemistry Lab Diagnostics Medical Fac; Düsseldorf, Germany