Key result
Ninjurin2 deficiency exacerbates injury-induced intimal hyperplasia and promotes VSMC phenotypic switching, whereas its overexpression attenuates this pathological remodeling.
Why the study?
Although NINJ2 polymorphisms are associated with atherosclerosis, ischemic stroke, and coronary artery disease, the functional role of Ninjurin2 in regulating vascular smooth muscle cell plasticity remained unexplored.
Does Ninjurin2 overexpression prevent injury-induced intimal hyperplasia in mice subjected to carotid artery ligation?
Does Ninjurin2 overexpression prevent injury-induced intimal hyperplasia in mice subjected to carotid artery ligation?
Ninjurin2 acts as a novel regulator of vascular smooth muscle cell phenotypic switching via the PDGFRβ/FAK axis, providing new mechanistic insights into vascular remodeling.
Answers are grounded in this paper and cite their sources.
Ninj2 modulates VSMC phenotypic switching; extends GWAS associations mechanistically but leaves therapeutic targeting open.
Vascular smooth muscle cell (VSMC) phenotypic switching from a contractile to synthetic state plays a pivotal role in vascular remodeling. Although genome-wide association studies have linked NINJ2 (encode Ninjurin2) polymorphisms are associated with risk of atherosclerosis and related conditions like ischemic stroke and coronary artery disease, its functional role in regulating VSMC plasticity remains unexplored. Here, using Ninj2 knockout ( Ninj2 -/- ) and smooth muscle-specific overexpressing ( Ninj2 smcTG ) mice subjected to carotid artery ligation, we demonstrate that Ninjurin2 deficiency exacerbates injury-induced intimal hyperplasia, whereas its overexpression attenuates this pathological remodeling. Mechanistically, Ninjurin2 knockdown promoted PDGF-BB-mediated VSMC phenotypic switching, proliferation, and migration, while biochemical studies revealed that Ninjurin2 interacts with PDGFRβ to suppress FAK signaling. These findings identify Ninjurin2 as a novel regulator of VSMC phenotypic switching via the PDGFRβ/FAK axis, offering new mechanistic insights into vascular remodeling and potential therapeutic avenues for atherosclerosis.
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Jia et al. (2025) studied Vascular remodeling and intimal hyperplasia. Ninjurin2 genetic modulation (knockout or overexpression) vs. Wild-type or control littermates was evaluated on Neointimal formation (intima-to-media ratio) and VSMC phenotypic switching (p=<0.01). Ninjurin2 deficiency exacerbates injury-induced intimal hyperplasia and promotes VSMC phenotypic switching, whereas its overexpression attenuates this pathological remodeling.
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