PRDM16 deficiency in vascular smooth muscle cells aggravates abdominal aortic aneurysm

• DOI: 10.1172/jci.insight.167041
• Publication Date: 2023-04-20T16:03:16Z
• Authors: Zhenguo Wang; Xiangjie Zhao; Guizhen Zhao; Yanhong Guo; Haocheng Lu; Wenjuan Mu; Juan Zhong; Minerva Garcia-Ba...; Jifeng Zhang; Y. Eugene Chen; Lin Chang
• Keywords: PRDM16

Abdominal aortic aneurysm (AAA) is usually asymptomatic until life-threatening complications occur, predominantly involving rupture. Currently, no drug-based treatments are available, primarily due to limited understanding of AAA pathogenesis. Transcriptional regulator PR domain-containing protein 16 (PRDM16) highly expressed in the aorta, but its functions aorta largely unknown. By RNA-seq analysis, we found that VSMCs-specific Prdm16 knockout mice (Prdm16SMKO) already showed extensive changes expression genes associated with extracellular matrix (ECM) remodeling and inflammation abdominal under normal housing conditions without any pathological stimuli. Human lesions displayed lower PRDM16 expression. Periadventitial elastase application suprarenal region aggravated formation Prdm16SMKO. During development, VSMCs undergo apoptosis because both intrinsic environmental including ECM remodeling. deficiency promoted VSMCs. A disintegrin metalloproteinase 12 (ADAM12) a gelatinase which can degrade various ECM. We ADAM12 target transcriptional repression by PRDM16. Adam12 knockdown reversed VSMC induced deficiency. Our study demonstrated aggravates formation, may provide potential targets for treatment.