Pregnancy-induced vascular remodelling: Changes in the structure and mechanical properties of the bovine thoracic aorta

• Main Author: DeBay, Drew Roderick
• Format: Dissertation
• Language: English
• Subjects: biology, animal physiology; engineering, biomedical
• ISBN: 9780494348499; 0494348496

There are striking changes in hemodynamic conditions in the maternal cardiovascular system during pregnancy, with blood volume increasing ∼40% over gestation and cardiac output increasing ∼50% by term. Arteries adapt to chronic changes in pressure and flow by adjusting vessel thickness and diameter to maintain tensile and shear stress, respectively. Hormonal cues (e.g. relaxin) during pregnancy may also trigger remodelling of cardiovascular tissues by modulating extracellular matrix constituents such as collagen. Surprisingly few studies have examined the adaptive remodelling of elastic arteries to pregnancy. Beyond evidence that modulation of tissue synthesis or degradation occurs, the remodelling mechanisms in general are poorly understood. This is the first study to examine the changes in structure and mechanical properties of the maternal thoracic aorta as it adapts to pregnancy. In so doing, we hope to further elucidate vascular remodelling mechanisms associated with pregnancy: an ideal model of "non-pathological", mature cardiovascular remodelling.
Aortae were harvested from non-pregnant heifers and early (101 days gestation) pregnant cows. Aortic ring dimensions were measured and mechanical properties were assessed via stress relaxation and quasi-static stress-strain tests. Separate aortic rings were cut for residual strain measurements of (i) whole and (ii) elastin purified rings. Hydrothermal Isometric Tension (HIT) tests were used to assess mechanically relevant collagen crosslinking in the aortic wall. Standard histological techniques were used to investigate aortic wall structure.
This study has demonstrated, for the first time, rapid remodelling in the aorta as it undergoes adaptations to pregnancy. Changes in dimensions, mechanical properties and residual stresses indicate structural remodelling to the aortic wall. In early pregnancy, aortic extensibility and residual stresses - largely held in elastin - increased, suggesting differential remodelling of elastic lamellae across the wall. Histological observations supported the idea that increased (faster) remodelling may occur at inner lamellae in pregnancy. The aorta increased in diameter, with constant wall thickness, which would result in elevated wall stress in vivo. Increased wall stress in late pregnancy may be a mechanical trigger that drives extensibility back to pre-pregnant values over this interval. The latter observation suggests a two-stage remodelling mechanism in aortic collagen that allows the network to lengthen and then regain its pre-pregnancy, crimp. Collagen crosslinking data demonstrated a paradoxical increase in collagen crosslinking with a near-absence of immature crosslinks in an expansively remodelling aorta.
This study sheds new light on vascular remodelling mechanisms and contradicts two long held beliefs, namely that (i) mature elastin has very low turnover and hence minimal capacity for remodelling and (ii) that remodelling of collagen networks is largely dependent on immature crosslinks that are able to break and reform allowing fibril extension while maintaining structural and mechanical properties. Instead, we have shown that mature elastic arteries are capable of remodelling in a non-pathological state via rapid remodelling of elastin. The remodelling of collagen via immature crosslinking mechanisms in the maternal aorta may have been "overridden" by the pregnancy hormone relaxin, which inhibits collagen synthesis and turnover.