Vascular inflammatory and lipid-related pathways

Vascular inflammatory and lipid-related pathways encompass the synergistic biological processes that drive the initiation and progression of atherosclerosis and subsequent cardiovascular events. The lipid-related component involves the dysregulation of lipoprotein metabolism, specifically the retention and oxidation of low-density lipoprotein (LDL) particles within the arterial intima [Ference et al., 2017]. This lipid accumulation triggers the inflammatory component, characterized by the activation of the NLRP3 inflammasome and the release of pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) [Ridker et al., 2017]. These pathways are intrinsically linked, as cholesterol crystals can act as endogenous danger signals that exacerbate vascular inflammation, leading to plaque instability [Libby, 2021]. Pharmacological intervention targets these pathways through lipid-lowering therapies like statins and PCSK9 inhibitors, as well as anti-inflammatory agents like colchicine [Nidorf et al., 2020]. Addressing both lipid levels and inflammatory status is a critical strategy for mitigating residual cardiovascular risk in patients who have already achieved target LDL levels. Clinical trials such as CANTOS and COLCOT have demonstrated that targeting the inflammatory arm of this axis can significantly reduce major adverse cardiovascular events (MACE) [Ridker et al., 2017; Tardif et al., 2019]. Consequently, these integrated pathways are central to modern cardiology and drug development for ischemic heart disease.

Other names

Atherosclerotic pathwaysLipid-inflammation axisResidual inflammatory risk pathwaysCardio-inflammatory pathways

Modulation of lipid metabolism through HMG-CoA reductase or PCSK9 inhibition and suppression of pro-inflammatory cytokine signaling via NLRP3 inflammasome or IL-1 beta antagonism.