Dissecting the Genomics of Spontaneous Coronary Artery Dissection

Weldy, Chad S.; Murtha, Ryan; Kim, Juyong Brian

doi:10.1161/circgen.122.003867

Cited by 1 publication

(1 citation statement)

References 27 publications

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“…In Marfan syndrome, for example, the pathological changes in the aortic root are thought to be related to angiotensin II receptor 1 (ART1) signaling and the reverse-remodeling effects of losartan are mediated by blocking ART1 signaling and downstream TGF-β signaling ( 259 ). Targeted delivery of TGF-β inhibitory peptides has also recently been suggested as a potential future therapeutic for SCAD ( 260 ). Importantly, these stimuli are known to alter cellular identity, increasing cellular activation in ECs and VSMCs, and to alter the ECM ( 36 , 46 ).…”

Section: Discussion – Common Features Of Dissectionsmentioning

confidence: 99%

Arterial dissections: Common features and new perspectives

Bax

Romanov

Junday

et al. 2022

Front. Cardiovasc. Med.

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Arterial dissections, which involve an abrupt tear in the wall of a major artery resulting in the intramural accumulation of blood, are a family of catastrophic disorders causing major, potentially fatal sequelae. Involving diverse vascular beds, including the aorta or coronary, cervical, pulmonary, and visceral arteries, each type of dissection is devastating in its own way. Traditionally they have been studied in isolation, rather than collectively, owing largely to the distinct clinical consequences of dissections in different anatomical locations – such as stroke, myocardial infarction, and renal failure. Here, we review the shared and unique features of these arteriopathies to provide a better understanding of this family of disorders. Arterial dissections occur commonly in the young to middle-aged, and often in conjunction with hypertension and/or migraine; the latter suggesting they are part of a generalized vasculopathy. Genetic studies as well as cellular and molecular investigations of arterial dissections reveal striking similarities between dissection types, particularly their pathophysiology, which includes the presence or absence of an intimal tear and vasa vasorum dysfunction as a cause of intramural hemorrhage. Pathway perturbations common to all types of dissections include disruption of TGF-β signaling, the extracellular matrix, the cytoskeleton or metabolism, as evidenced by the finding of mutations in critical genes regulating these processes, including LRP1, collagen genes, fibrillin and TGF-β receptors, or their coupled pathways. Perturbances in these connected signaling pathways contribute to phenotype switching in endothelial and vascular smooth muscle cells of the affected artery, in which their physiological quiescent state is lost and replaced by a proliferative activated phenotype. Of interest, dissections in various anatomical locations are associated with distinct sex and age predilections, suggesting involvement of gene and environment interactions in disease pathogenesis. Importantly, these cellular mechanisms are potentially therapeutically targetable. Consideration of arterial dissections as a collective pathology allows insight from the better characterized dissection types, such as that involving the thoracic aorta, to be leveraged to inform the less common forms of dissections, including the potential to apply known therapeutic interventions already clinically available for the former.

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