The response-to-retention hypothesis: From theory to the potential therapeutic approaches

The key initiating process in atherogenesis is the subendothelial retention of apolipoprotein B-containing lipoproteins. Retained lipoproteins are chemically and enzymatically modified, inducing a chronic inflammatory response. Therapeutic approaches for atherosclerosis treatment have been focused on the control of risk factors, such as hypercholesterolemia, hypertension, and diabetes mellitus. Nonetheless, the efficacy of these strategies is limited and unfortunately the health problem persists. On the other hand, development of therapies targeting the interactions between low-density lipoproteins and components of the extracellular matrix has been poorly addressed. In this work, we review the response-to-retention hypothesis and the recent data on therapeutic approaches targeting the retentive process of proatherogenic low-density lipoproteins.