stabilisation des plaques. Rôle de l’inflammation

Journal des Maladies Vasculaires nants, IDL and LDL) penetrate the arterial intima and undergo retention, thus favoring cholesterol accumulation and atherosclerotic plaque formation. Despite the success of statin therapy in lowering atherogenic lipoprotein levels and thereby reducing cardiovascular morbimortality by up to 35% across a broad range of dyslipidaemic phenotypes in both primary and secondary prevention trials, demonstration of significant regression of atherosclerotic plaques in coronary arteries has been infrequent. Indeed, even in recent intervention trials involving intensive lipid lowering therapy in patients with coronary atherosclerosis, reduced atheroma progression -rather than significant plaque regression - was predominantly observed. What key mechanistic features might account for these findings? Potent statins act primarily to reduce circulating concentrations of atherogenic, apoB-containing lipoproteins (VLDL, VLDL remnants, IDL and LDL) by up to 50% or more. By contrast, statins fail to induce elevation in HDL to a similar degree, and indeed statin-induced raising of HDL cholesterol levels is typically in the range of 5-10%. Clearly then, statins are efficacious in reducing cholesterol influx into the arterial wall in the form of atherogenic lipoproteins, but do not appear to induce elevation of HDL to levels facilitating maximal efflux of cholesterol from cholesterol-rich atherosclerotic plaques. Indeed maximal rates of arterial cholesterol efflux to HDL concomitant with marked reduction in cholesterol influx and accumulation would be predicted to lead to significant plaque regression. In this context, it is especially relevant that recent in vivo findings in patients with acute coronary syndromes clearly suggest that infusion of HDL mimetic particles containing apoAI and phospholipids can lead to significant and rapid reduction of coronary atheroma plaque volume consistent with lesion regression. Such reduction in disease burden is suggestive of significant improvement in long term clinical outcome. Considered together, these findings clearly indicate that marked elevation of HDL-C may be a critical component of atherosclerosis regression. HDL therefore represents a key therapeutic target in atherogenic dyslipidae-

mia, a proposal consistent with epidemiological data (Framingham, PROCAM, ARIC) which have revealed that there is a potent and progressive reduction of coronary artery disease risk with increasing HDL-C levels.

Mots-cle's : LipoprotCines de haute densite (HDL). RCgression de la plaque d3athCrome.

FRAGILISATION/STABILISATION ROLE DE L'INFLAMMATION

DES

PLAQUES.

Z. MALLAT INSERM U 541, H6pital Lariboisik.re, Paris. Atherosclerosis is an inflammatory disease of the arterial wall that carries an important socio economic burden. The available data strongly suggest that both innate and adaptive immuno inflammatory mechanisms are the major determinants of plaque complications (called instability). Therefore, most of the important advances in the comprehension of the mechanisms of atherosclerosis came from studies that aimed at the elucidation of the critical components involved in the modulation of the immuno inflammatory response in experimental models of atherosclerosis. Since Thl-driven immune response has been consistently shown to promote atherosclerosis, the general belief is that immuno-modulation through Th2 may be suitable to halt the disease process. Here, we present a novel view of the immuno-inflammatory response in atherosclerosis where the adaptive regulatory response modulates both Thl and Th2 responses and plays a central role in counteracting disease initiation and progression.

Mots-clks :Atherosclerosis. Inflammation.