Role of CARD8 for inflammation in vascular cells

Every year, more than 17 million of people die from cardiovascular diseases and atherosclerosis is an important underlying factor. The atherosclerotic process is initiated in the early childhood and a hallmark is chronic inflammatory processes in the atherosclerotic lesions.

One of the central molecules in the inflammatory process in atherosclerotic lesions is CARD8 (also known as TUCAN/CARDINAL). CARD8 has in earlier studies been identified as a negative regulator of NF-κB and caspase-1. In some studies, CARD8 has been associated with the NLRP3 inflammasome, although we could not verify that CARD8 affects the IL-1β release in vascular smooth muscle cells (Tangi et al 2012). However, we have shown that CARD8 affects the release of downstream target proteins involved in inflammation, such as MCP-1, IL-6, CXCL1, CXCL6, PDGF-A and ALCAM (Paramel et al 2020).

The aim of the project is to understand how CARD8 is involved in inflammation and atherosclerosis, but also other biological processes. Identification of novel target molecules is very important and may in the future be used for tailored therapy against cardiovascular disease.