STABILIZATION OF ATHEROSCLEROTIC PLAQUE DURING LIPID-LOWERING

Lipid lowering therapy leads to a great reduction of cardiovascular co mplications, but has almost no effect on the degree of stenosis of cor onary arteries. These findings have lead to a new paradigm of coronary artery disease, i. e. clinical prognosis is not only determined by th e extent of a single stenosis, but mainly by the number and structure of atherosclerotic plaque. Rupture of an instable or vulnerable plaque , characterized by a large lipid-rich central core, inflammatory cells , and a thin fibrous cap, causes sudden thrombus formation and thereby acute coronary syndromes. There is accumulating evidence that cholest erol lowering can result in plaque stabilization and improvement of en dothelial dysfunction, reviewed recently in this journal. Accordingly, this review focuses on new molecular mechanisms which provide evidenc e that reduction of cellular cholesterol activates novel transcription factors, called sterol regulatory element binding proteins, which can regulate not only the LDL receptor, thereby reducing plasma cholester ol levels, but also a diverse number of other genes. These gene regula tory events might link cholesterol lowering not only to cellular chole sterol metabolism, but also to triglyceride metabolism, cell different iation and other events potentially stabilizing vulnerable plaque.