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Genetic influence on vascular smooth muscle cell apoptosis.
- Source :
-
Cell death & disease [Cell Death Dis] 2024 Jun 08; Vol. 15 (6), pp. 402. Date of Electronic Publication: 2024 Jun 08. - Publication Year :
- 2024
-
Abstract
- Vascular smooth muscle cell (VSMC) proliferation, migration, and apoptosis play important roles in many physiological processes and pathological conditions. To identify genetic influences on VSMC behavior, we measured these traits and undertook genome-wide association studies in primary umbilical artery-derived VSMCs from >2000 individuals. Although there were no genome-wide significant associations for VSMC proliferation or migration, genetic variants at two genomic loci (7p15.3 and 7q32.3) showed highly significant associations with VSMC apoptosis (P = 1.95 × 10 <superscript>-13</superscript> and P = 7.47 × 10 <superscript>-9</superscript> , respectively). The lead variant at the 7p51.3 locus was associated with increased expression of the GSDME and PALS2 genes in VSMCs. Knockdown of GSDME or PALS2 in VSMCs attenuated apoptotic cell death. A protein co-immunoprecipitation assay indicated that GSDME complexed with PALS2. PALS2 knockdown attenuated activated caspase-3 and GSDME fragmentation, whilst GSDME knockdown also reduced activated caspase-3. These findings provide new insights into the genetic regulation of VSMC apoptosis, with potential utility for therapeutic development.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Genome-Wide Association Study
Caspase 3 metabolism
Caspase 3 genetics
Cell Proliferation genetics
Membrane Proteins metabolism
Membrane Proteins genetics
Cell Movement genetics
Cells, Cultured
Apoptosis genetics
Muscle, Smooth, Vascular metabolism
Muscle, Smooth, Vascular cytology
Myocytes, Smooth Muscle metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 15
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 38851795
- Full Text :
- https://doi.org/10.1038/s41419-024-06799-z