Recent advances in the field of cardiovascular medicine have emphasized the involvement of inflammation in the formation of atherosclerotic plaque. Our understanding of cardiovascular disease (CVD) is in a constant stage of evolution. It has been shown that inflammatory signals at the site of plaque initiation attract monocytes from the circulation into the vascular wall to form lipid-laden foam cells and promote smooth muscle cell proliferation, resulting in plaque progression. It is for this reason that emerging strategies focus on inhibiting cellular proliferation and pro-inflammatory mediators of monocyte migration.
We have taken the strategic step to expand the NexVas franchise. The NexVas™ Vascular Inflammation (NexVas VI) program is a discovery stage technology for the development of drugs that target molecular markers of inflammation.
Please mouse over the interactive image to learn about the vascular inflammation pathway.
1. LDL from the circulation enters the arterial wall where it is oxidized and begins to accumulate.
2. Oxidized LDL along with other factors (not shown) stimulate endothelial cells to express adhesion molecules such as VCAM-1 on their surface, which bind circulating monocytes.
3. Monocytes migrate into the arterial wall, following concentrations of chemoattractants such as MCP-1.
4. Once in the arterial wall, monocytes mature into activated macrophages, which express scavenger receptors which bind oxidized LDL.
5. Macrophages internalize the oxidized LDL particles giving rise to foam cells.
6. Activated macrophages or foam cells secrete pro-inflammatory cytokines, reactive oxygen species, matrix metalloproteinases and other factors which exacerbate the inflammatory process, as well as result in smooth muscle cell proliferation and migration.
7. Foam cells, dead macrophages, lipids and smooth muscle cells accumulate to form a fatty streak, eventually resulting in an atherosclerotic plaque.
