Segmental aortic stiffness determined by the association of elastin degradation and calcium deposition in rat models of hypertension and aortic calcification

Background: Aortic stiffness can be assessed by pulse wave velocity (PWV) and is determined by the integrity of elastin lamellae, elastin and collagen content and wall matrix constituents. This study investigates extracellular matrix changes in the thoracic and abdominal aorta in rat models of hyper- tension and aortic calcification. Methods: PWV was determined at 110 mmHg in spontaneously hypertensive (SHR) and normotensive rats (WKY), and in WKY induced with aortic calcification by vitamin D and nicotine injection (VDN); 6 rats in each group. Thoracic and abdominal aortic segments were perfusion fixed (110mmHg) and processed for calcium quantification and histological staining for elastin and collagen. An elastin fragmentation index was obtained as a percentage of fractured lamellae. Results: Compared with WKY, both SHR and VDN showed higher PWV in the thoracic aorta (Table), but only VDN showed higher PWV in the abdominal aorta. Both VDN and SHR showed lower density of inter- lamellar elastin but not collagen content in the thoracic aorta, resulting in lower elastin/collagen ratio in the thoracic (SHR and VDN) and abdominal aorta (VDN) compared with WKY. Greater degree of elastin lamellae fragmentation was observed in the thoracic aorta of SHR and in abdominal aorta of VDN, both associated with increased calcium content. Conclusion. Aortic stiffness is determined by elastin degradation, in addition to blood pressure, in hypertension and aortic calcification. Findings are consistent with elastin fragmentation being a possible stimulus for trans- differentiation of smooth muscle cell phenotype, leading to increased calcium deposition in the arterial wall.