Miscellaneous Item
Authors: Karl T. Weber
Journal: Cardiovascular Research (1997)

CardioOascular Research introduced a Cardiovascular w x Mystery Series several years ago 1 . Included amongst its Ž . objectives: a an exploration of less well known aspects of Ž . cardiovascular disease; b an integration of basic and Ž . clinical sciences and c an intention to be provocative. A clinical vignette, in the form of a mystery story, sets the stage for an invited mini-review on a topic that addresses these objectives. As Series Editor, I was delighted when Professor of Pathology, William E. Stehbens, found the w x vignette ‘Vascular aneurysms: a side-splitting affair’ 2 and its patients M. and F. sufficiently provocative to bring forward his views in a Letter to the Editor entitled ‘The pathogenesis of arterial aneurysms and associated lesions’. Drawing on traditional concepts, Stehbens has emphasized the importance of ‘hemodynamic biomechanical stress’ in promoting such iterations in vascular architecture. He indicates ‘‘...aneurysms develop when intravascular pressure is greater than the wall can withstand...’’ and ‘‘...aneurysms indicate mural weakness’’. I completely concur with the latter—an intrinsic defect in the tensile strength of the vessel wall is responsible for its aneurysmal dilatation—and would add that such loss of vascular integrity is not based on prevailing andror repetitive surges in intraluminal pressure. Hypertension is not a prerequisite; it does predispose to aneurysmal dilatation in a weakened vessel. Aneurysms complicate many different diseases and clearly do not have a single pathogenic origin. Potential causes include abnormal structural protein phenotype and proteinase-mediated degradation of such proteins as collagen and elastin. One would not confuse the pathogenesis of aneurysmal dilatation seen in inherited connective tissue Ž . disorders e.g., Marfan’s syndrome with that associated with acquired atherosclerotic disease. In the mini-review w x that follows the vignette 3 , Herron provides a compelling argument for the involvement of matrix metalloproteinases in the formation of abdominal aortic aneurysm. Stehbens goes on to discuss patient M. with adult dominant polycystic kidney disease and correctly indicates that it is unknown whether proteinase activity is increased in the aneurysms of the cerebral circulation that appear in this entity. This is also true for abdominal aortic aneurysm, dissecting aneurysm of the thoracic aorta, mitral valve prolapse and intestinal diverticula associated with this inherited disorder. There likewise is no documented evidence for abnormal structural protein phenotype in this entity. However, does it not seem likely that either scenario would explain this unusual predisposition to ‘weakness’ in these diverse tissues whose fibrillar type I collaw x gen should have the tensile strength of steel 4 ? Weightlifters experience sudden and marked increments in arterial pressure during isometric exercise, but they experience neither mitral valve prolapse nor arterial aneurysm. Aneurysmal formation appears subsequent to emboli of myxomatous tissue as was the case in patient F. In contrast to septic or bland emboli, such tumor emboli contain pluripotent cells, such as the myofibroblast phenotype w x 5,6 . These cells can express proteinases that account for their ability to invade vascular tissue with destruction of w x elastic lamina and media 7,8 . These emboli resemble the metastatic behavior of neoplastic tissue, where proteinase w x activation is an integral feature 9 . Even after removal of the tumor embolus, the continued presence of such cells within the invaded vessel leads to its destruction with w x subsequent aneurysmal formation 10 . In closing, a localized defect in tissue tensile strength leads to its distention. This is expressed as aneurysmal dilatation in the case of blood vessels, diverticula of the intestine and prolapse of valve leaflets. To implicate hypertension, a hemodynamic condition present throughout the arterial vasculature and left ventricular chamber, as the predominant causal mechanism for localized tissue weakness is no longer tenable and unwarranted, in my opinion. We are what we know and we see what we want according