Fokin Alexander A, Robicsek Francis, Cook Joseph W, Thubrikar Mano J, Schaper Jutta
Department of Thoracic and Cardiovascular Surgery, Heineman Medical Research Laboratories, Carolinas Medical Center, 1000 Blythe Blvd., Charlotte, NC 28203, USA.
J Heart Valve Dis. 2004 May;13(3):444-51.
Age-related loss of elasticity of the naturally compliant aortic root disrupts the coordinated function of the valve leaflets. Morphological changes that developed over time in the aortic valve leaflets of non-compliant aortic roots were studied.
Stiffening of the aortic roots was achieved in vivo by applying Super Glue around the sinus of Valsalva in 27 New Zealand White rabbits. In nine animals, glue was applied only partially, and eight untreated rabbits served as controls. Histological evaluation of the aortic valves was performed at 8-11 months after surgery, and included immunohistochemistry and confocal microscopy with quantitative tissue assessment. Levels of collagen I, as a main component of fibrosis, and matrix metalloproteinases (MMP)-1 and MMP-9 and angiotensin-converting enzyme (ACE), as regulators of fibrosis, were analyzed. The morphological structure of the aortic valve leaflets was studied, and the length, thickness and area of leaflets were measured.
Leaflects in all groups were found to be composed of a continuous layer of collagen fibers at the mural side, and loose connective tissue containing fibroblasts and few capillaries on the aortic luminal aspect. In stiffened aortic roots, the length and area of the leaflets were increased. The area occupied by collagen was elevated in non-compliant aortic root leaflets, but collagen fluorescence intensity was decreased, indicating less densely packed collagen fibers. Degradation and synthesis of collagen as reflected by MMP-1, MMP-9 and ACE levels was up-regulated.
Loss of compliance in aortic roots leads to elongation of the leaflets which, combined with a decrease in collagen density, may render leaflets more susceptible to mechanical stress. In time, this may promote the development of degenerative changes in the aortic valve.
随着年龄增长，自然顺应性主动脉根部弹性丧失会破坏瓣叶的协调功能。本研究对非顺应性主动脉根部瓣叶随时间发生的形态学变化进行了研究。
通过在27只新西兰白兔的主动脉瓣窦周围涂抹强力胶，在体内实现主动脉根部硬化。9只动物仅部分涂抹胶水，8只未处理的兔子作为对照。术后8 - 11个月对主动脉瓣进行组织学评估，包括免疫组织化学和共聚焦显微镜检查以及定量组织评估。分析了作为纤维化主要成分的I型胶原蛋白、作为纤维化调节因子的基质金属蛋白酶（MMP）-1、MMP-9和血管紧张素转换酶（ACE）的水平。研究了主动脉瓣叶的形态结构，并测量了瓣叶的长度、厚度和面积。
所有组的瓣叶在壁侧均由连续的胶原纤维层组成，在主动脉腔侧含有成纤维细胞和少量毛细血管的疏松结缔组织。在硬化的主动脉根部，瓣叶的长度和面积增加。非顺应性主动脉根部瓣叶中胶原蛋白所占面积升高，但胶原蛋白荧光强度降低，表明胶原纤维排列较疏松。MMP-1、MMP-9和ACE水平反映的胶原蛋白降解和合成上调。
主动脉根部顺应性丧失导致瓣叶伸长，再加上胶原蛋白密度降低，可能使瓣叶更容易受到机械应力影响。随着时间推移，这可能促进主动脉瓣退行性变的发展。
