Figure 1.

All roads lead to Rome: vascular inflammation. Multiple pro-inflammatory pathways can participate in triggering and amplifying endothelial dysfunction, offering multiple venues to explore, target wise. IL-1 pathway blockade offers three targets worth exploring: blocking the cytokine (canakinumab), its receptor (anakinra) or IL-1 receptor antagonist therapy. In regards to cholesterol synthesis, besides the obvious hypolipemic effect observed with statins, it can also be argued that they lower geranyl-geranyl-pyrophosphate, and in this, lowering Rac1 activation. Ergo, farnesylation inhibition is also an attractive target for oxidative stress control. As for immunization, conventional and experimental vaccines have been proposed. Rac1 activation it’s common pathway of endothelial inflammation for C. pneumoniae, so a pathogen-specific therapeutic vaccine is viable target. Vaccines against neoantigens such as ApoB100, and specific common epitopes which are conserved even after LDL modification, are underway. Finally, using ApoA1 mimetics is a direct way to accelerate and increase the efficacy of reverse cholesterol transport. IL, interleukin; TNF-α, tumor necrosis factor-α; Rac1, Ras-related C3 botulinum toxin substrate 1; SMC, smooth muscle cell; VLDL, very low-density lipoprotein; HDL, high density lipoprotein; LDL, low density lipoprotein; mLDL, modified low density lipoprotein; ApoB100, apolipoprotein B100; HMG-CoA, hydroxy-methyl-glutaryl coenzyme A; NLRP3, Nod-like receptor family pyrin domain containing 3; NF-κβ, nuclear factor-κβ; JNK, c-Jun N-terminal kinase; p38, p38 mitogen-activated protein kinases.