Scavenger receptors (SRs) are a ‘superfamily’ of membrane-bound receptors that were initially thought to bind and internalize modified low-density lipoprotein (LDL), though it is currently known to bind to a variety of ligands including endogenous proteins and pathogens. New family of SRs and their properties have been identified in recent years, and have now been classified into 10 eukaryote families, defined as Classes A-J. These receptors are classified according to their sequences, although in each class they are further classified based in the variations of the sequence. Their ability to bind a range of ligands is reflected on the biological functions such as clearance of modified lipoproteins and pathogens. SR members regulate pathophysiological states including atherosclerosis, pathogen infections, immune surveillance, and cancer. Here, we review our current understanding of SR structure and function implicated in health and disease.

Lectin-like oxidized low-density lipoprotein receptor-1 (SR-E1, LOX-1, OLR1) was first discovered as a vascular receptor for modified lipoprotein particles nearly 20 years ago. Since then, in vitro and in vivo studies have demonstrated an association between LOX-1, a soluble form (sLOX-1) and a number of diseases including atherosclerosis, arthritis, hypertension and pre-eclampsia. However, converting such discoveries into tools and drugs for routine clinical use is dependent on translational preclinical and clinical studies but such studies have only begun to emerge in the past decade. In this review, we identify the key clinical applications and corresponding criteria that need to be addressed for the effective use of LOX-1-related probes and molecules for patient benefit in different disease states.

data in CHD cases will be a productive means of identifying causative genes. In this study we have undertaken various refinement steps to narrow down potentially causative candidate gene/s within deleted (DEL) and duplicated (DUP) CNV regions that have been previously shown to be highly associated with non-syndromic CHD patients. Firstly, we have generated case DEL and DUP CNV lists. This was done by updating a published meta-analysis study (our group have contributed to this study) though utilisation of DECIPHER, ISCA, ECARUCA databases and published studies, using different key terms to identify further non-syndromic CHD patients. We then utilised BedTools to compare these case lists with the corresponding control CNV lists generated by using controls from published literature, DECIPHER, the Database of Genomic Variants and the 1000Genome Phase 3 CNVs. The resulting unique cases CNV regions were annotated and compared against an in-house list of candidate genes (containing novel or rare variants) generated from an exome data analysis of 850 Tetralogy of Fallot (ToF) patients. Genes were further prioritised based on whether they have already an assigned human phenotype, on their ExAC CNV scores, probability of haploinsufficiency (pHI) and loss of function (LoF) intolerance scores. Initially, we have identified 10 586 genes for which 1986 genes are present in both DEL and DUP CNV regions, 2772 genes are unique in DUP and 3842 genes unique in DEL regions (Figure 1). Further analysis of genes in DEL regions and genes present in both types of CNVs revealed that 1,150/3,842 genes and 588/1,986 genes respectively have LoF variants in our ToF exome data. Additional filtering with pHI and pLI scores resulted in 57 genes collectively. This is an on-going work and our plan is to design a next-generation sequencing panel to screen our final candidate gene list in an additional 2000 CHD cases. We will focus on the most promising candidate gene emerging from the discovery experiment to perform functional work. Our experimental strategy will vary depending on what is known about the gene, and whether its involved or not in any well-known signalling pathway during heart development such as the Wnt and VEGF pathways.