Scavenger receptors act as membrane-bound and soluble proteins that bind to macromolecular complexes and pathogens. This diverse supergroup of proteins mediates binding to modified lipoprotein particles which regulate the initiation and progression of atherosclerotic plaques. In vascular tissues, scavenger receptors are implicated in regulating intracellular signaling, lipid accumulation, foam cell development, and cellular apoptosis or necrosis linked to the pathophysiology of atherosclerosis. One approach is using gene therapy to modulate scavenger receptor function in atherosclerosis. Ectopic expression of membrane-bound scavenger receptors using viral vectors can modify lipid profiles and reduce the incidence of atherosclerosis. Alternatively, expression of soluble scavenger receptors can also block plaque initiation and progression. Inhibition of scavenger receptor expression using a combined gene therapy and RNA interference strategy also holds promise for long-term therapy. Here we review our current understanding of the gene delivery by viral vectors to cells and tissues in gene therapy strategies and its application to the modulation of scavenger receptor function in atherosclerosis.
Cardiovascular disease is the leading cause of death. The disease is due to atherosclerosis which is characterized by lipid and fat accumulation in arterial blood vessel walls. A key causative event is the accumulation of oxidised low density lipoprotein particles within vascular cells, and this is mediated by scavenger receptors. One such molecule is the LOX-1 scavenger receptor that is expressed on endothelial, vascular smooth muscle, and lymphoid cells including macrophages. LOX-1 interaction with OxLDL particles stimulates atherosclerosis. LOX-1 mediates OxLDL endocytosis via a clathrin-independent internalization pathway. Transgenic animal model studies show that LOX-1 plays a significant role in atherosclerotic plaque initiation and progression. Administration of LOX-1 antibodies in cellular and animal models suggest that such intervention inhibits atherosclerosis. Antiatherogenic strategies that target LOX-1 function using gene therapy or small molecule inhibitors would be new ways to address the increasing incidence of vascular disease in many countries.
Introduction As the veterinary profession has become feminised, gender discrimination and its effects have been documented in practicing veterinary surgeons. However, research on gender discrimination experienced by veterinary students and its effects on recruitment and retention remains limited. This study aimed to increase understanding of veterinary students’ experiences of gender discrimination and its impact on their career aspirations. Methods A questionnaire including statements with Likert‐style response options and free‐text questions was distributed to students studying veterinary medicine and science at a UK veterinary school in September 2020 (28% response rate). Two focus groups were carried out following the questionnaire to gain a deeper insight into student experiences. Results Gender discrimination in a veterinary setting had been experienced by 34% of respondents, the majority (77%) on animal husbandry placements. Female students were more likely to report that their experiences of gender discrimination affected their career aspirations. Seven themes were identified from both the questionnaire and focus group data: stereotyping of certain fields, gender inequality on placements, the lesbian, gay, bisexual, transgender, queer and intersex, plus (LGBTQI+) community, encouraging reporting behaviours, barriers to reporting, education and the placement allocation. Conclusions This study highlighted that gender discrimination was prevalent during animal husbandry placements, although reporting was infrequent and perceived negatively by students. Recommendations on how veterinary schools and the wider veterinary profession can support veterinary students are made as an outcome of this work.
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