Preclinical study reveals that REDD1 silencing worsens aortic dissection by driving vascular smooth muscle cell apoptosis, indicating a protective compensatory role for REDD1.
Key Points
To determine the role and underlying molecular mechanism of REDD1 in vascular smooth muscle cell apoptosis and aortic dissection progression.
Analyzed human single-cell RNA-sequencing data (GSE222318) to evaluate REDD1 expression, apoptosis, and autophagy markers in aortic tissue.
Silenced REDD1 using adeno-associated virus via tail-vein injection in C57BL/6J mice subjected to BAPN-induced aortic dissection.
Assessed apoptosis, mitochondrial membrane potential, and autophagy/mTOR signaling pathways in cultured vascular smooth muscle cells using Western blotting, JC-1 staining, and flow cytometry.
REDD1 expression was significantly upregulated in human aortic dissection tissues, localizing primarily to medial vascular smooth muscle cells.
Knockdown of REDD1 in mice exacerbated aortic dissection pathology, accompanied by increased levels of BAX and p62 and decreased levels of BCL-2 and LC3B.
Silencing REDD1 in vascular smooth muscle cells elevated p-mTOR, triggered loss of mitochondrial membrane potential, and accelerated apoptosis, effects that were rescued by rapamycin.