The class
Review highlights CETP inhibition improving survival in a mouse model of sepsis (Curr Opin Lipidol 2026)
Original title: HDL-associated proteins affecting CVD and systemic inflammation
This review examines how HDL-associated proteins, rather than HDL cholesterol level alone, determine HDL's protective capacity against inflammation and cardiovascular disease. Among the mechanisms discussed, the review highlights a study in which HDL-bound endotoxin is degraded through the endosome-lysosome pathway in an SR-B1-dependent manner, attenuating IL-1 beta activation, and in which inhibition of cholesteryl ester transfer protein (CETP) increased HDL and improved mortality in a mouse model of sepsis. The authors note this finding highlights the therapeutic potential of CETP inhibition, a pathway currently being tested in key clinical trials, alongside other emerging HDL-function mechanisms including the role of ApoM in chronic kidney disease and ApoA-I, SAA, and SR-B1 in preventing arterial LDL entrapment.
Original abstract
Purpose Of Review: It has become clear that elevated HDL-C is not a reliable marker of protection against inflammation and cardiovascular disease (CVD). This review summarizes recent advances in understanding how HDL function is affected by its associated proteins, demonstrating that this is a more appropriate lens through which to assess HDL's protective capacity.
Recent Findings: Recent publications have demonstrated an inverse relationship between ApoM and clinical outcomes in chronic kidney disease and its concomitant cardiovascular indications. Mechanistic studies show that ApoM's regulation of mitochondrial function and autophagy are likely contributors to this effect. Additionally, ApoA-I, serum amyloid albumin (SAA), and SR-B1 have recently been highlighted as key regulators of atherogenesis through their ability to prevent LDL transcytosis and arterial entrapment by proteoglycans. Lastly, a novel mechanism is described wherein HDL-bound endotoxin is degraded through the endosome-lysosome pathway in an SR-B1-dependent manner, attenuating IL-1β activation. In the same study, inhibition of CETP (cholesterol ester transfer protein) increased HDL and improved mortality in a mouse model of sepsis, highlighting this pathway's importance and therapeutic potential of CETP inhibition, which is currently in key clinical trials.
Summary: HDL regulates inflammation and CVD through a variety of mechanisms independent of reverse cholesterol transport, including autophagy, LDL deposition, endotoxin clearance.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.