Author + information
- Tiziano M. Scarabellia,b,
- Mahmoud Ismaila,b,
- Alessio Rungatschera,b,
- Mebratu Alebachew Gebriea,b,
- Giovanni Battista Luciania,b,
- Riccardo Raddinoa,b,
- Louis Saravolatza,b,
- Carol Chen-Scarabellia,b and
- Giuseppe Faggiana,b
Background: Opioid receptors include four major subtypes, i.e. mu (MOR), delta (DOR), kappa (KOR), and nociceptin receptor (NOR), all of which G protein-coupled receptors. Prior studies carried out both in animal models and the human hearts have shown that opioid receptor activation induces cardioprotection. Although it is well known that diabetic patients (DMPs) undergoing on-pump cardiac surgery (OPCS) have higher morbidity and mortality than non-diabetic patients (NDMPs), the molecular mechanisms responsible for the reported worse outcomes remain unknown.
Objectives: The present study investigated the expression levels of DOR and KOR in the right atrium of DMPs and NDMPs undergoing OPCS.
Methods: A total of 20 sequential biopsy specimens were obtained from the right atrium of 10 DMPs and 10 NDMPs before cardiopulmonary bypass and 10 minutes after release of the aorta cross-clumping. The expression levels of DOR and KOR RNA and protein were evaluated by Real-Time (RT) PCR, as well as Western Blotting (WB) and immunohistochemistry, respectively.
Results: By RT-PCR and WB analysis, DOR and KOR RNAs and proteins were detected in all samples from DMPs and NDMPs. Cytosolic and perinuclear expression of DOR and KOR proteins was detected by immunohistochemistry (IHC) in 55±6% of cardiac cells from DMPs and in 53±8% of myocytes from NDMPs (p>0.05). Colocalization of DOR and KOR proteins was observed in the majority of cardiac cells (87±11% in DMPs and 82±8% in NDMPs; p>0.05). A significant induction of both DOR and KOR RNAs and proteins was observed in all reperfused specimens, as compared to basal levels (p<0.01). Likewise, cellular expression of DOR and KOR proteins, as assessed by IHC, consensually increased to 74±8% and 71±6% in myocytes from DMPs and NDMPs, respectively (p<0.01; p>0.05 in comparing DMPs vs NDMPs).
Conclusions: The expression DOR and KOR RNAs and proteins significantly increased after cardioplegic arrest and reperfusion, as compared to basal levels. However, no difference in expression was found between DMPs and NDMPs. Further experiments are warranted to verify whether postcardioplegic induction of DOR and KOR RNAs can affect myocytes survival in either patient population.
Poster Hall, Hall C
Saturday, March 18, 2017, 9:45 a.m.-10:30 a.m.
Session Title: From Diet to Drugs: Mechanistic Insight Into Ischemic Heart Disease
Abstract Category: 1. Acute and Stable Ischemic Heart Disease: Basic
Presentation Number: 1202-298
- 2017 American College of Cardiology Foundation