Atherosclerosis--where are we heading?
Aim of this review is, to analyse the current knowledge of the pathogenesis of atherosclerosis from the viewpoint of a clinical cardiologists. All the current ideas about the pathogenesis of atherosclerosis have been derived from the theories of three pathologists. The first was Rokitanski 1852, his theory was somewhat modified by Virchow 1856 and revitalised and modified again by Ross in 1986. All current theories however are based on the term response to injury leading to accelerated atherosclerosis. Following the classification of Stary et al. and the suggestions of the report of the Committee on Vascular Lesions of the Council of Arteriosclerosis the early lesions (Stary class I and II) should be renamed as normal vascular adaptation to physical or chemical causes. These causes include not only shears stress or turbulences due to increased blood pressure but also hypercholesterolemia and certain changes of plasma protein content. The classification of Fuster et al. is mainly dependent on a mechanical injury to the arterial wall induced by the interventional cardiologist. Thus far, it seems questionable, if such a response to injury is indeed the leading mechanism ultimately resulting in advanced arteriosclerosis. In view of the multifactorial processes involved in the pathogenesis of either adaptation or then accelerated arteriosclerosis we have to admit, that our insight is still limited. Thus far, the only lesson to be learned for practising clinicians is that we have to accept that the process of normal adaptation of the vascular arterial wall to the abnormal development of a clinical significant lesion is dynamic and is not well characterized by the response-to-injury theory. We do know that even in the stage of acute coronary syndromes lesion changes are unpredictable. This coincides with the finding from the experimental laboratory that lesion growth is episodic and a result of different stages of activity of the involved cell types and growth factors. Thus, we should avoid looking only for certain stages but rather accept that this is 1. a normal adaptative alteration of the arterial wall which might 2. result in accelerated atherosclerosis due to genetic determination of smooth muscle cells and accumulation of a variety of growth factors.
Karsch
K R
KR
Medizinische Klinik, Universität Tübingen.
D000818:Animals; D002455:Cell Division / Q000502:physiology; D003324:Coronary Artery Disease / Q000503:physiopathology* / Q000628:therapy; D004730:Endothelium, Vascular / Q000503:physiopathology; D005544:Forecasting; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D010973:Platelet Adhesiveness / Q000502:physiology; D012008:Recurrence