Unveiling cellular and molecular aspects of ascending thoracic aortic aneurysms and dissections.
Berta H GanizadaRogier J A VeltropAsim C AkbulutRory R KoenenRyan AccordRoberto LorussoJos G MaessenKoen ReesinkElham BidarLeon J SchurgersPublished in: Basic research in cardiology (2024)
Ascending thoracic aortic aneurysm (ATAA) remains a significant medical concern, with its asymptomatic nature posing diagnostic and monitoring challenges, thereby increasing the risk of aortic wall dissection and rupture. Current management of aortic repair relies on an aortic diameter threshold. However, this approach underestimates the complexity of aortic wall disease due to important knowledge gaps in understanding its underlying pathologic mechanisms.Since traditional risk factors cannot explain the initiation and progression of ATAA leading to dissection, local vascular factors such as extracellular matrix (ECM) and vascular smooth muscle cells (VSMCs) might harbor targets for early diagnosis and intervention. Derived from diverse embryonic lineages, VSMCs exhibit varied responses to genetic abnormalities that regulate their contractility. The transition of VSMCs into different phenotypes is an adaptive response to stress stimuli such as hemodynamic changes resulting from cardiovascular disease, aging, lifestyle, and genetic predisposition. Upon longer exposure to stress stimuli, VSMC phenotypic switching can instigate pathologic remodeling that contributes to the pathogenesis of ATAA.This review aims to illuminate the current understanding of cellular and molecular characteristics associated with ATAA and dissection, emphasizing the need for a more nuanced comprehension of the impaired ECM-VSMC network.
Keyphrases
- vascular smooth muscle cells
- extracellular matrix
- pulmonary artery
- aortic valve
- aortic dissection
- cardiovascular disease
- left ventricular
- risk factors
- angiotensin ii
- healthcare
- pulmonary hypertension
- coronary artery
- aortic aneurysm
- spinal cord
- pulmonary arterial hypertension
- neoadjuvant chemotherapy
- randomized controlled trial
- genome wide
- type diabetes
- metabolic syndrome
- physical activity
- locally advanced
- dna methylation
- heart failure
- spinal cord injury
- coronary artery disease
- weight loss
- lymph node
- single molecule
- cardiovascular events
- cardiovascular risk factors
- rectal cancer
- optical coherence tomography
- stress induced