This study found that although increased ILT is associated with lower MWS and PWS, it is also associated with aneurysm rupture at smaller diameters and lower stress. Therefore, the protective biomechanical advantage that ILT provides by lowering wall stress seems to be outweighed by weakening of the AAA wall, particularly in patients with small rAAAs. This study suggests that high ILT burden may be a surrogate marker of decreased aortic wall strength and a characteristic of high-risk small aneurysms.
Hemodynamic conditions play a critical role in embryonic cardiovascular development, and altered blood flow leads to congenital heart defects. Chicken embryos are frequently used as models of cardiac development, with abnormal blood flow achieved through surgical interventions such as outflow tract (OFT) banding, in which a suture is tightened around the heart OFT to restrict blood flow. Banding in embryos increases blood pressure and alters blood flow dynamics, leading to cardiac malformations similar to those seen in human congenital heart disease. In studying these hemodynamic changes, synchronization of data to the cardiac cycle is challenging, and alterations in the timing of cardiovascular events after interventions are frequently lost. To overcome this difficulty, we used ECG signals from chicken embryos (Hamburger-Hamilton stage 18, ∼3 days of incubation) to synchronize blood pressure measurements and optical coherence tomography images. Our results revealed that, after 2 h of banding, blood pressure and pulse wave propagation strongly depend on band tightness. In particular, while pulse transit time in the heart OFT of control embryos is ∼10% of the cardiac cycle, after banding (35% to 50% band tightness) it becomes negligible, indicating a faster OFT pulse wave velocity. Pulse wave propagation in the circulation is likewise affected; however, pulse transit time between the ventricle and dorsal aorta (at the level of the heart) is unchanged, suggesting an overall preservation of cardiovascular function. Changes in cardiac pressure wave propagation are likely contributing to the extent of cardiac malformations observed in banded hearts.
We demonstrate that AOO, PAD, and COPD in AAA are associated with rAAAs at smaller diameters. AOO appears to increase PWS, whereas COPD and PAD may be surrogate markers of decreased aortic wall strength. We therefore recommend consideration of early, elective AAA repair in patients with AOO, PAD, or COPD to minimize risk of early rupture.
Marfan syndrome (MFS) is a highly variable genetic connective tissue disorder caused by mutations in the calcium binding extracellular matrix glycoprotein fibrillin-1. Patients with the most severe form of MFS (neonatal MFS; nMFS) tend to have mutations that cluster in an internal region of fibrillin-1 called the neonatal region. This region is predominantly composed of eight calcium-binding epidermal growth factor-like (cbEGF) domains, each of which binds one calcium ion and is stabilized by three highly conserved disulfide bonds. Crucially, calcium plays a fundamental role in stabilizing cbEGF domains. Perturbed calcium binding caused by cbEGF domain mutations is thus thought to be a central driver of MFS pathophysiology. Using steered molecular dynamics (SMD) simulations, we demonstrate that cbEGF domain calcium binding decreases under mechanical stress (i.e. cbEGF domains are mechanosensitive). We further demonstrate the disulfide bonds in cbEGF domains uniquely orchestrate protein unfolding by showing that MFS disulfide bond mutations markedly disrupt normal mechanosensitive calcium binding dynamics. These results point to a potential mechanosensitive mechanism for fibrillin-1 in regulating extracellular transforming growth factor beta (TGFB) bioavailability and microfibril integrity. Such mechanosensitive “smart” features may represent novel mechanisms for mechanical hemostasis regulation in extracellular matrix that are pathologically activated in MFS.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.