Scavenger receptors and their potential as therapeutic targets in the treatment of cardiovascular disease.

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.

Antiplatelet agents and risk factors for bleeding postcarotid endarterectomy.

BACKGROUND: Antiplatelet therapy has been implicated as a risk factor for wound hematoma formation after carotid endarterectomy (CEA). Given the increasing use of alternative antiplatelet drugs acting through differing inhibitory pathways, we audited the incidence of re-operation for bleeding post-CEA. METHODS: Data were prospectively recorded on all patients undergoing CEA in Leicester, United Kingdom between November 1997 and October 2001. The data from those requiring exploration for bleeding were studied on a case-controlled basis using paired age and sex-matched controls from within the overall database. Assessment of the patients' demographics, drug history, and intraoperative and postoperative care was made. RESULTS: A total of 448 patients were reviewed and 27 (6.03%) cases of postoperative bleeding were identified which required exploration. Despite the prevalent use of antiplatelet drugs before surgery, there was no increased risk of bleeding associated with their use identified on univariate analysis. Patients who underwent re-exploration for bleeding had a significantly greater prevalence of post-CEA hypertension (21/27 cases vs. 25/54 controls, respectively; p = 0.014). Patients who underwent surgical re-exploration for bleeding also had a greater transfusion requirement (1.33 ± 1.3 vs. 0.02 ± 0.1 units; p ≤ 0.0001) and a longer hospital stay (4.9 ± 2.2 days vs. 2.9 ± 2.3 days; p = 0.001) although there was no increase in morbidity or mortality. CONCLUSION: The use of newer antiplatelet drugs before surgery was not associated with an increased risk of bleeding after CEA in this study. Tight control of blood pressure, both pre- and postsurgery, appears to be important, and a protocol for the management of this condition is recommended.