Abdominal aortic aneurysm (AAA), is a complex disorder characterized by vascular vessel wall remodeling. LIGHT (TNFSF14) is a proinflammatory cytokine associated with vascular disease. In the present study, the impact of genetic inactivation of
Light was investigated in dissecting AAA induced by angiotensin
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Abdominal aortic aneurysm (AAA), is a complex disorder characterized by vascular vessel wall remodeling. LIGHT (TNFSF14) is a proinflammatory cytokine associated with vascular disease. In the present study, the impact of genetic inactivation of
Light was investigated in dissecting AAA induced by angiotensin II (AngII) in the Apolipoprotein E-deficient (
Apoe−/−) mice. Studies in aortic human (ah) vascular smooth muscle cells (VSMC) to study potential translation to human pathology were also performed. AngII-treated
Apoe−/−Light−/− mice displayed increased abdominal aorta maximum diameter and AAA severity compared with
Apoe−/− mice. Notably, reduced smooth muscle α-actin+ area and
Acta2 and
Col1a1 gene expression were observed in AAA from
Apoe−/−Light−/− mice, suggesting a loss of VSMC contractile phenotype compared with controls. Decreased
Opn and augmented
Sox9 expression, which are associated with detrimental and non-contractile osteochondrogenic VSMC phenotypes, were also seen in AngII-treated
Apoe−/−Light−/− mouse AAA. Consistent with a role of LIGHT preserving VSMC contractile characteristics, LIGHT-treatment of ahVSMCs diminished the expression of
SOX9 and of the pluripotency marker
CKIT. These effects were partly mediated through lymphotoxin β receptor (LTβR) as the silencing of its gene ablated LIGHT effects on ahVSMCs. These studies suggest a protective role of LIGHT through mechanisms that prevent VSMC trans-differentiation in an LTβR-dependent manner.
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