Making Things Stick in the Fight Against Atherosclerosis

Abstract

Prevention of atherosclerotic vascular disease through systemic risk factor management has had great success, but cardiovascular disease is still the leading cause of death. One approach to this treatment gap is complementary arterial wall–based therapy that inhibits either the trigger of atherosclerosis, lipoprotein retention, or its pathobiological consequences, nonresolving inflammation. A recent article by Kastrup et al describes a technical advance that brings this approach closer to reality. The investigators have developed and validated a drug-eluting adhesive biogel that has the durability and stability to provide chronic therapy directly to plaques in the setting of pulsatile arterial blood flow. This advance expands the opportunity to develop drugs that retard atherosclerotic plaque progression and promote plaque resolution and regression. Currently available therapeutic strategies directed against atherosclerotic vascular disease focus primarily on reducing systemic risk factors, notably hyperlipidemia, diabetes mellitus, smoking, and hypertension. Lipid therapy, particularly with statins, is very effective, because it lowers the probability that apolipoprotein B100–containing lipoproteins (apoB LPs) will enter and be retained in susceptible regions of the arterial wall, which is the trigger for the pathobiological responses that initiate and promote atherogenesis.1 Indeed, if we could imagine a world where everyone’s plasma apoB LP level was maintained at a very low level starting in the early teenage years, which is the age at which atherosclerotic lesions usually first appear, the current leading cause of death would be close to nonexistent.2 However, although tremendous progress has been made in reducing heart disease, this ultimate goal is currently unachievable due to the difficulty of implementing effective lifestyle changes and limitations related to drug safety and compliance. Therefore, translational biomedical researchers have turned their attention to complementary approaches that target atherogenic processes in the arterial wall. It is in this context that we can appreciate a technical advance …