Vaccination against TIE2 reduces atherosclerosis

Area of Science:

• Cardiovascular Research
• Immunology
• Vascular Biology

Background:

• TIE2-expressing cells are integral to angiogenesis, a process implicated in atherosclerosis.
• Targeting TIE2-expressing cells via DNA vaccination presents a potential strategy to modulate atherosclerosis development.

Purpose of the Study:

• To investigate the efficacy of DNA vaccination targeting TIE2-expressing cells in reducing atherosclerosis.
• To assess the impact of this vaccination strategy on cellular immunity, lesion size, plaque stability, and angiogenesis.

Main Methods:

• An oral DNA vaccination technique using attenuated Salmonella typhimurium carrying plasmid pcDNA3.1 encoding TIE2 was employed in LDLr(-/-) mice.
• Mice received three oral vaccinations before being placed on a Western-type diet to induce atherosclerosis.

Main Results:

• Vaccination against TIE2 significantly reduced circulating TIE2(+) cells by 33%, confirming successful cellular immunity induction.
• Significant reductions in carotid atherosclerosis (30% intima area, 27% intima/lumen ratio) and aortic root atherosclerosis (42%) were observed.
• Adventitial angiogenesis decreased by 61%, and plaque collagen content increased (1.6-1.9 fold), indicating enhanced plaque stability.

Conclusions:

• Vaccination against TIE2 effectively induces cellular immunity and attenuates atherosclerotic lesion development.
• This vaccination strategy promotes a more stable plaque phenotype and may offer a novel therapeutic approach for atherosclerosis.