By Christina Villard and Rebecka Hultgren
The impact of gender on abdominal aortic aneurysm is illustrated by both the differences in prevalence and in the progression of the disease between the sexes. The male dominance in the occurrence of abdominal aortic aneurysms suggests that the aortic wall in men is more prone to dilatation or that the one in women is resistant to it. On the other hand, the increased rupture risk reported in women with abdominal aortic aneurysms suggests that the aneurysm wall of women is less resistant, possibly due to differences in the biomechanical properties of the aneurysm wall.
The biomechanical properties of the aneurysm wall can be ascribed to its structural components: elastin, collagen and vascular smooth muscle cells (VSMCs). They are all affected by the degradation resulting in aneurysm disease, yet there is little knowledge of how these structural elements are altered in abdominal aortic aneurysms of women and potentially differ from aneurysms in men. A potential difference in the structural components of the aortic wall between the sexes could help explain why men are more susceptible to abdominal aortic aneurysm formation and women with aneurysms more prone to rupture.
The impact of gender on aneurysm formation has been illustrated in animal models. Several studies report a preventive effect of estrogen by inhibition of the proteolytic activity in the aneurysm wall. Gender has also been associated with the changes occurring in the abdominal aorta with increasing age. A less pronounced age-related change in the abdominal aorta of women, ie. less pronounced increase of aortic diameter and vessel wall stiffness have been associated with an effect of female sex hormones. Thereto female sex hormones have been shown to reduce collagen deposition as opposed to testosterone that increases it. The biomechanical properties of the aneurysm wall can be ascribed to its structural components: elastin, collagen and vascular smooth muscle cells. They are all affected by the degradation resulting in aneurysm disease, yet there is little knowledge of how these structural elements are altered in abdominal aortic aneurysms of women and how they potentially differ from those in aneurysms in men. Potential differences in the structural components of the aortic wall between the sexes could help explain why men are more susceptible to aneurysm formation and women with abdominal aortic aneurysms more prone to rupture.
There is little knowledge of potential gender differences in the structural elements of both the aortic and aneurysm wall in humans. In one of two recent reports, Tong et al described a lower amount of elastin in the thrombus-covered aneurysm wall of men compared with women and an opposite relation for collagen. In a recent study by our group the results of a lower amount of elastin in the thrombus covered aneurysm wall in men could not be confirmed. Instead we found an increased expression of elastolytic enzymes and a simultaneous lower expression of elastin in the non-thrombus-covered aneurysm wall of women compared with men. Differences in the expression of elastin and elastolytic enzymes between men and women with abdominal aortic aneurysms could have implications for the difference in aneurysm progression between the sexes.
The reported fourfold, increased rupture risk in women with abdominal aortic aneurysms compared with men could be explained by a greater relative aneurysm enlargement in women and/or reduced wall strength in the aneurysm wall of women, as has been illustrated in finite element models. With the fragmentation of elastin the aortic wall loses it elasticity, still it is the failure of collagen that deprives the aorta of its principal load-bearing capacity and ultimately ruptures. The greater rupture risk in women together with the observation that aneurysm rupture occurs much earlier in the course of the disease in women makes the collagen biosynthesis and potential gender differences therein of special interest. Thereto, differences in apoptotic stimuli and extent of inflammation might be of importance for differences in biomechanical properties. Preliminary results from our group suggest that there are differences but also similarities in these structural elements between men and women with abdominal aortic aneurysms between the sexes.
It is clear that in order to understand the pathophysiological gender differences resulting in different prevalence rates, growth rates and rupture risk between the sexes, vessel wall analyses are needed. The difference in prevalence between men and women with abdominal aortic aneurysms might be related to fundamental differences in the aortic wall of men and women. The gender difference in rupture risk might be related to a less resistant aneurysm wall of women, due to either a more pronounced degradation or inherent differences in the comparatively few women that develop aneurysms.
Christina Villard and Rebecka Hultgren are with the Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden