Photoactivatible HDL and its transport in experimental psoriasis

Lipoproteins trapped in arteries drive atherosclerosis. Extravascular LDL ligates LDL receptor for cellular uptake, whereas HDL interacts with cells to pick up cellular cholesterol, and then recirculates to plasma. We developed photoactivatable apoA-I to understand how HDL passage through tissue is regulated. We focused on skin and arteries of healthy mice versus those with psoriasis, which carries cardiovascular risk in man. Our findings suggest that immunity, programmed in lymph nodes draining inflamed skin, allows for IL-17-producing T cells to home to distal skin and later to arteries, where little pathology is observed except remodeling of collagenous matrix, such that larger molecules generally become entrapped. HDL transit was rescued by depleting CD4+ T cells, neutralizing IL-17, or inhibiting lysyl oxidase that crosslinks collagen. Experimental psoriasis was systemically associated with vascular stiffness and increased atherosclerosis, also driven by IL-17. Thus, IL-17 can reduce lipoprotein trafficking by, at least in part, remodeling collagen.