An Apoptotic Failsafe Program Involving PDGF-dependent PI 3-Kinase Activity Contributes to Plaque Composition in Atherosclerosis

Chronically elevated PDGFRβ signaling in LDLR-/-smLRP1-/- mice unexpectedly increases VSMC apoptosis in atherosclerotic plaques, and PI3K binding is required for this pro-apoptotic effect.

• Why it matters: Growth-factor–dependent PI3K activation is thought to suppress VSMC apoptosis, but its role under chronically elevated PDGFRβ signaling during atherogenesis is unclear.
• What they did: Atherosclerosis was assessed in LDLR-/-smLRP1-/- mice with PDGFRB overexpression, and VSMC apoptosis and downstream signaling were tested in cultured aortic VSMCs; PDGFRβ-F2/F2 mutation and PI3K isoform analyses were used.
• The result: PDGF showed transient anti-apoptotic effects but long-term stimulation promoted death; PI3K p110 supported survival while p110δ and p110β promoted apoptosis, via PI3K-dependent c-Myc induction that suppresses Bcl-2.