C-Kit Is Essential for Vascular Smooth Muscle Cell Phenotypic Switch In Vitro and In Vivo After Injury

Area of Science:

• Vascular Biology
• Cellular Plasticity
• Regenerative Medicine

Background:

• Pathological vascular remodeling underlies diseases like atherosclerosis and restenosis.
• Vascular smooth muscle cell (VSMC) phenotypic switching is central to this remodeling.
• The role of receptor tyrosine kinase c-Kit in VSMC plasticity remains unclear.

Purpose of the Study:

• To investigate the role of c-Kit in VSMC phenotypic switching and vascular repair.
• To determine if c-Kit deficiency impacts VSMC proliferation, differentiation, and senescence.
• To assess the therapeutic potential of modulating c-Kit for vascular diseases.

Main Methods:

• Utilized c-Kit haploinsufficient mice and primary aortic VSMC cultures.
• Employed carotid artery ligation (CAL) model for in vivo studies.
• Analyzed gene expression (RNA-Seq), cell proliferation (BrdU, Ki67), and senescence markers (p16INK4a, p21).

Main Results:

• c-Kit haploinsufficiency impaired the contractile-to-synthetic VSMC transition and blunted PDGF-BB-induced proliferation.
• c-Kit deficiency promoted VSMC senescence and suppressed cell-cycle activation post-injury.
• Reduced neointima formation and impaired re-endothelialization were observed in c-Kit haploinsufficient mice.

Conclusions:

• c-Kit acts as a critical gatekeeper for VSMC plasticity and reparative responses.
• Adequate c-Kit signaling promotes VSMC proliferation and differentiation from progenitors.
• Modulating c-Kit may offer a strategy to balance vascular repair and pathological remodeling.