Hypercholesterolemia and inflammation in atherogenesis: two sides of the same coin.
An abundance of experimental, clinical, and epidemiologic data capped by stunning interventional results with the statins has established hypercholesterolemia as a major causative factor in atherogenesis. In familial hypercholesterolemia and in animal models it is a sufficient cause. Some degree of hypercholesterolemia, perhaps 30-50 mg/dL, may even be a necessary cause. It is equally clear that from the very beginning atherogenesis has a strong inflammatory component, i. e., it is characterized by penetration of monocytes and of T-cells into the developing lesion. These cells, through the secretion of cytokines and growth factors, through immune responses, and through complex cross-talk with elements of the artery wall modulate the growth of the lesion and affect its stability. But inflammation has to occur in response to something. What is that something? What is the "injury" in "response-to-injury"? The case will be made that oxidized lipids in oxidized LDL or generated in response to prooxidative changes in the cells of the artery wall should be considered a plausible candidate. There is no need to consider hypercholesterolemia and inflammation as alternative hypotheses. Both are very much involved. Optimal intervention and prevention will probably require attention to both.
Steinberg
Daniel
D
University of California San Diego, La Jolla, CA 92093-0682, USA. dsteinberg@ucsd.edu
D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000209:etiology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000150:complications*; D006938:Hyperlipoproteinemia Type II / Q000150:complications; D007249:Inflammation / Q000150:complications*; D008077:Lipoproteins, LDL; D009000:Monocytes / Q000473:pathology / Q000502:physiology; D013601:T-Lymphocytes / Q000473:pathology / Q000502:physiology
D016207:Cytokines; D006133:Growth Substances; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein