54 The nlrp3 inflammasome and other related receptors as potential biomarkers in coronary artery disease (cad) and major adverse cardiac events (mace)


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Abstract

IntroductionCoronary artery disease (CAD) is the leading cause of death worldwide caused by atherosclerosis, now believed to be a complex inflammatory process. Mounting data indicates that the Nucleotide-binding domain, leucine-rich containing family, pyrin domain-containing-3 (NRLP3) inflammasome is critical in the pathogenesis and/or regulation of a variety of inflammatory diseases including atherosclerosis. NLRP3 is a multiprotein complex responsible for the activation of capase-1 and proteases required for processing and activating IL-1 b and IL-18. Previous evidence suggests that NLRP3 is activated and regulated by the cannabinoid receptor type 1 (CB1 r) and scavenger receptor, cell surface cluster of differentiation 36 (CD36 r) in response to modified lipoproteins through amplification of inflammation or exposure to oxidised low-density lipoproteins (oxLDL). CB1 r and CD36 r are therefore considered risk factors for atherosclerosis, in the promotion of cholesterol accumulation and release of inflammatory mediators. To date, no study has investigated NLRP3, CD36 r and CB1 r collectively as a potential panel of biomarkers to predict major adverse cardiovascular events (MACE).PurposeTo measure the expression of the NLRP3 inflammasome and associated receptors (CD36 r and CB1 r) and to determine if levels correlate with cardiovascular risk.MethodsConsecutive patients were recruited from the cardiac catheterisation laboratory and outpatient clinics. Group 1 were defined as Very high risk patients (VHR) with a 10-year risk SCORE ≥10% risk of fatal CVD. VHR patients were subdivided in Acute Coronary Syndrome patients (ACS-VHR) and elective percutaneous coronary intervention patients (ELEC-VHR). Group 2 were low risk patients (LR) with a 10-year risk SCORE <1% risk of fatal CVD. Proteins were extracted from a buffy coat preparation using the Mammalian Protein Extraction Reagent (M-PER) and then analysed by western blot. RNA was extracted from the buffy coat and analysed by real time PCR.ResultsA total of 60 patients were recruited and the cohort consisted of VHR (n=40), which were divided into ACS-VHR (n=20) and ELEC-VHR (n=20), and LR (n=20). NLRP3 gene expression was higher in VHR compared to LR (0.0284 ± 0.0013 vs. 0.0142 ± 0.0019, p<0.0001). NLRP3 protein levels were also higher in VHR compared to LR (p<0.05). NLRP3 gene and protein levels were particularly higher in ACS-VHR compared to LR (p<0.05). CB1 r protein levels were higher in VHR compared to LR (p<0.01). CD36 R gene expression was not significantly between VHR and LR, however protein levels were significantly different.ConclusionThese results indicate that NLRP3 and CB1 r can potentially differentiate between VHR and LR patients. An ongoing larger cohort study is underway to investigate the utility of NLRP3, CD36 r and CB1 r along with other promising biomarkers to better predict CAD and MACE.

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