Research Article| Volume 74, SUPPLEMENT 1, S11-S15, June 30, 2000

Download started.


Plaque stabilization: the role of lipid lowering


      The unstable atheroma characteristically has a thin, eccentric fibrous cap and a large necrotic core of lipid and cellular debris. This plaque configuration is particularly unstable because large mechanical stresses develop in the thinnest portions of the fibrosis cap over the lipid pool. Numerous recent observations tell us that critical biological factors other than lesion morphology also contribute to the ultimate fracture of the fibrous cap. Matrix-degrading enzymes, particularly members of the metalloproteinase family, are overexpressed in atherosclerotic tissue. The regions with the greatest amounts of these enzymes are the critical high stress regions, which are usually also infiltrated with inflammatory cells. At the cellular level a number of factors regulate expression of these enzymes by vascular smooth muscle cells. These factors include mechanical stimuli and cytokines known to be overexpressed in atheroma by both smooth muscle cells and macrophages. Low density lipoprotein cholesterol in the lesion plays a significant role in most or all of these processes, and our current understanding of the unstable atheroma is consistent with the dramatic clinical successes of lipid-lowering therapy.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to International Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Davies M.J.
        • Bland J.M.
        • Hangartner J.R.W.
        • Angelini A.
        • Thomas A.C.
        Factors influencing the presence or absence of acute coronary artery thrombi in sudden ischaemic death.
        Eur Heart J. 1989; 10: 203-208
        • Falk E.
        Progressive atherogenesis: why do plaques rupture?.
        Circulation. 1992; 86: III30-III42
        • Lee R.T.
        • Libby P.
        The unstable atheroma.
        Arterioscler Thromb Vasc Biol. 1997; 17: 1859-1867
        • Topol E.J.
        • Nissen S.E.
        Our preoccupation with coronary luminology: the dissociation between clinical and angiographic findings in ischemic heart disease.
        Circulation. 1995; 92: 2333-2342
        • Ambrose J.A.
        • Tannenbaum M.A.
        • Alexopoulos D.
        • et al.
        Angiographic progression of coronary artery disease and the development of myocardial infarction.
        J Am Coll Cardiol. 1988; 12: 56-62
        • Richardson P.D.
        • Davies M.J.
        • Born G.V.R.
        Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques.
        Lancet. 1989; 2: 941-944
        • Loree H.M.
        • Kamm R.D.
        • Stringfellow R.G.
        • Lee R.T.
        Effects of fibrous cap thickness on peak circumferential stress in model atherosclerotic vessels.
        Circ Res. 1929; 71: 850-858
        • Geng Y.
        • Libby P.
        Evidence for apoptosis in advanced human atheroma: colocalization with interleukin-1β-converting enzyme.
        Am J Pathophysiol. 1995; 147: 251-266
        • Bennett M.R.
        • Evan G.I.
        • Schwartz S.M.
        Apoptosis of rat vascular smooth muscle cells is regulated by p53-dependent and -independent pathways.
        Circ Res. 1995; 77: 266-273
        • Van Der Wal A.C.
        • Becker A.E.
        • Van Der Loos C.M.
        • Das P.K.
        Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology.
        Circulation. 1994; 89: 36-44
        • Lee E.
        • Grodzinsky A.J.
        • Libby P.
        • Clinton S.K.
        • Lark M.W.
        • Lee R.T.
        Human vascular smooth muscle cell-monocyte interactions and metalloproteinase secretion in culture.
        Arterioscler Thromb Vasc Biol. 1995; 15: 2283-2289
        • Shah P.K.
        • Falk E.
        • Badimon J.J.
        • et al.
        Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques: potential role of matrix-degrading metalloproteinases and implications for plaque rupture.
        Circulation. 1995; 92: 1565-1569
        • Ridker P.M.
        • Cushman M.
        • Stampfer M.J.
        • Tracy R.P.
        • Hennekens C.H.
        Inflammation, aspirin and the risk of cardiovascular disease in apparently healthy men.
        New Engl J Med. 1997; 336: 973-979
        • Steinberg D.
        Oxidative modification of LDL and atherogenesis.
        Circulation. 1997; 95: 1062-1071
        • Anderson T.J.
        • Meredity I.T.
        • Yeung A.C.
        • Frei B.
        • Selwyn A.P.
        • Ganz P.
        The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion.
        New Engl J Med. 1995; 332: 488-493
        • Rosenson R.S.
        • Tangney C.C.
        Antiatherothrombotic properties of statins: implications for cardiovascular event reduction.
        J Am Med Assoc. 1998; 279: 1643-1650
        • Aikawa M.
        • Rabkin E.
        • Okada Y.
        • et al.
        Lipid lowering by diet reduces matrix metalloproteinase activity and increases collagen content of rabbit atheroma: a potential mechanism of lesion stabilization.
        Circulation. 1998; 97: 2433-2444
        • Loree H.M.
        • Tobias B.J.
        • Gibson L.J.
        • Kamm R.D.
        • Small D.M.
        • Lee R.T.
        Mechanical properties of model atherosclerotic lesion lipid pools.
        Arterioscler Thromb. 1994; 14: 230-234
        • Weber C.
        • Erl W.
        • Weber K.S.C.
        • Weber P.C.
        HMG-CoA reductase inhibitors decrease CD11b expression and CD11b-dependent adhesion of monocytes to endothelium and reduce increased adhesiveness of monocytes isolated from patients with hypercholesterolemia.
        J Am Coll Cardiol. 1997; 30: 1212-1217
        • Hebert P.R.
        • Gaziano J.M.
        • Chan K.S.
        • Hennekens C.H.
        Cholesterol lowering with statin drugs, risk of stroke and total mortality.
        J Am Med Assoc. 1997; 278: 313-321