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J Heart Lung Transplant. 2017 Jun;36(6):657-665. doi: 10.1016/j.healun.2016.12.007. Epub 2016 Dec 23.

Chemokine receptor patterns and right heart failure in mechanical circulatory support.

Author information

1
Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
2
School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
3
Heart and Vascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
4
Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
5
Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
6
Heart and Vascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
7
Heart and Vascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Electronic address: simonma@upmc.edu.

Abstract

BACKGROUND:

Right ventricular failure (RVF) complicates 9% to 44% of left ventricular assist device (LVAD) implants post-operatively. Current prediction scores perform only modestly in validation studies, and do not include immune markers. Chemokines are inflammatory signaling molecules with a fundamental role in cardiac physiology and stress adaptation. In this study we investigated chemokine receptor regulation in LVAD recipients who develop RVF.

METHODS:

Expression of chemokine receptor (CCR) genes 3 to 8 were examined in the peripheral blood of 111 LVAD patients, collected 24 hours before implant. RNA was isolated using a PAXgene protocol. Gene expression was assessed using a targeted microarray (RT2 Profiler PCR Array; Qiagen). Results were expressed as polymerase chain reaction (PCR) cycles to threshold and normalized to the average of 3 control genes, glyceraldehyde phosphate dehydrogenase (GAPDH), hypoxanthine phosphoribosyltransferase 1 (HPRT1) and β2-microglobulin (B2M). Secondary outcomes studied were 1-year mortality and long-term RV failure (RVF-LT).

RESULTS:

CCR3, CCR4, CCR6, CCR7 and CCR8 were downregulated in LVAD recipients with RVF. Within this cohort of patients, CCR4, CCR7 and CCR8 were further downregulated in those who required RV mechanical support. In addition, under-expression of CCR3 to CCR8 was independently associated with an increased risk of mortality at 1 year, even after adjusting for RVF. CCR expression did not predict RVF-LT in our patient cohort.

CONCLUSIONS:

Pre-LVAD CCR downregulation is associated with RVF and increased mortality after implant. Inflammatory signatures may play a major role in prognostication in this patient population.

KEYWORDS:

chemokine receptor; inflammation; left ventricular assist device; prognostication; right ventricular failure; survival

PMID:
28209402
PMCID:
PMC5446283
DOI:
10.1016/j.healun.2016.12.007
[Indexed for MEDLINE]
Free PMC Article

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