Atherosclerosis is a smooth muscle cell-driven tumor-like disease

Area of Science:

• Cardiovascular Biology
• Cancer Biology
• Inflammation Research

Background:

• Atherosclerosis is a chronic inflammatory cardiovascular disease driven by pathological cell activation.
• Smooth muscle cell (SMC) phenotypic switching is implicated in atherosclerosis, but underlying mechanisms remain unclear.

Approach:

• Utilized SMC lineage tracing mice for comprehensive molecular, cellular, histological, and computational profiling.
• Conducted genetic and pharmacological studies, including SMC-specific oncogenic Kras expression.
• Investigated the anti-cancer drug niraparib's effect on atherosclerosis progression and regression.

Key Points:

• SMC-derived cells in atherosclerosis exhibit tumor cell characteristics: genomic instability, immortality, proliferation, invasiveness, and cancer-associated gene networks.
• Oncogenic Kras accelerates SMC switching and worsens atherosclerosis.
• Niraparib, a DNA damage repair inhibitor, reduced atherosclerosis progression and induced lesion regression in mouse models.

Conclusions:

• Atherosclerosis exhibits significant tumor-like biological features in SMCs.
• This finding deepens understanding of atherosclerosis pathogenesis.
• Presents novel therapeutic strategies targeting DNA damage repair for atherosclerotic cardiovascular disease.