Coronary disease & ACSCohort study
Pathology of Genetic Variants in Spontaneous Coronary Artery Dissection
- Autopsy registry study
- whole-exome sequencing
- immunostaining
Authors' conclusion
Reduced medial collagen and smooth muscle cell phenotypic modulation may be possible predisposing conditions for SCAD, regardless of the presence of pathogenic or likely pathogenic variants. The presence of pathogenic variants in extracellular matrix-related genes may further compromise arterial wall medial integrity, contributing to more severe disease. These findings provide novel pathological and genetic insights into the pathogenesis of SCAD and may inform future diagnostic and therapeutic strategies.
Study context
- Population
- Spontaneous coronary artery dissection (SCAD) cases selected from the CVPath Autopsy Registry
- Participants
- 28 SCAD cases
- Exposure
- Histological differences in collagen and smooth muscle cells among culprit SCAD (C-SCAD), nonculprit SCAD and non-SCAD controls
Main finding
As reported in the abstract
- Significantly reduced in C-SCAD lesions compared with controls; no significant difference between C-SCAD and nonculprit SCAD
Observational data: associations, not effects.
Further findings
Smoothelin immunohistochemical staining in the media
- Reduced in the media of C-SCAD lesions compared with controls; no significant difference between C-SCAD and nonculprit SCAD
Nuclear height/width ratio of smooth muscle cells
- Increased, suggesting smooth muscle cell phenotypic modulation
Pathogenic or likely pathogenic variants (whole-exome sequencing)
- Cases with pathogenic or likely pathogenic variants
- 25%
- Higher frequency of multivessel dissection in these cases
Medial protein expression in cases with variants in COL3A1, FBN1 or FLNA
- Expression of the corresponding protein reduced in the media
Original publication
Summarised from the published abstract; every number is checked against it