Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids, fibrous elements, and cellular debris in the blood vessels. The response-to-retention hypothesis, the lea Show more
Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids, fibrous elements, and cellular debris in the blood vessels. The response-to-retention hypothesis, the leading theory on the pathogenesis of this cardiovascular disease, describes the initial event in atherosclerosis as when Apolipoprotein B-containing lipoproteins, including endogenous and dietary-derived lipoproteins, bind to the inner arterial wall, the tunica intima. The subsequent lipoprotein modifications trigger an immune response that promotes atherosclerotic plaque formation. Despite the prevalence of atherosclerosis globally, and its vascular nature, therapies directed to the artery wall are limited. Immunotherapies, most notably monoclonal antibodies (mAbs), are of special interest due to their high specificity, reliability and proven success in a variety of diseases. However, current mAbs for atherosclerosis tend to target disease risk factors, notably inflammation and circulating lipoprotein levels, rather than address the root cause of atherosclerosis. These treatments result in a phenomenon known as residual risk, defined by the occurrence of severe cardiovascular events, including myocardial infarction, during treatment. Per the "response to retention" hypothesis, a plausible strategy for atherosclerosis would be blocking cholesterol retention Show less