Correspondence
1998; Elsevier BV; Volume: 153; Issue: 4 Linguagem: Inglês
10.1016/s0002-9440(10)65677-5
ISSN1525-2191
Autores Tópico(s)Atherosclerosis and Cardiovascular Diseases
ResumoAtherosclerosis is the leading cause of death in the developed societies, probably related in part to relatively high-fat diets. The leading risk factor for the disease, however, is aging. A study of 19 different ethnic population groups demonstrated approximately linear rates of increases (although with different slopes) in the extent to which the intimal surfaces of aging aortas and coronary arteries develop raised, fibrotic, lipid-containing atheromas.1Eggen DA Solberg LA Variation of atherosclerosis with age.Lab Invest. 1968; 18: 571-579PubMed Google Scholar The great majority of deaths from atherosclerosis (typically via myocardial infarctions) occur after the age of 45. Quantitative studies2Hamilton WD The moulding of senescence by natural selection.J Theor Biol. 1966; 12: 12-45Crossref PubMed Scopus (1489) Google Scholar, 3Charlesworth B Evolution in age-structured populations. Cambridge University Press, New York1994Crossref Google Scholar, 4Martin GM Austad SN Johnson TE Genetic analysis of aging: role of oxidative damage and environmental stresses.Nat Genet. 1966; 13: 25-34Crossref Scopus (540) Google Scholar have demonstrated that genetic alleles responsible for phenotypes that are expressed beyond this age essentially fail to contribute to the gene pool of successive generations, thus escaping the force of natural selection. These alleles, however, may have been under strong selective pressure during earlier phases of the life course. This phenomenon has been referred to as “antagonistic pleiotropy” or “negative pleiotropy.”5Williams GC Evol. 1957; 11: 398-411Crossref Google Scholar, 6Rose MR Evolutionary biology of aging. Oxford University Press, New York1991Google Scholar I suggest that atherosclerosis may fall into this category of gene action and that its remarkably high prevalence in our species is a result of strong selective pressures for the retention of genes that enhance reproductive fitness early in the life course despite their deleterious effects on the vascular system postreproductively. It is likely that others have entertained or published such notions. One purpose of this correspondence is to ask my colleagues to inform me about the scientific history of this idea, which, it seems to me, is of seminal importance to the incipient discipline of evolutionary medicine.7Williams GC Nesse RM The dawn of Darwinian medicine.Q Rev Biol. 1991; 66: 1-22Crossref PubMed Scopus (467) Google Scholar The second purpose of this communication is to point out recent experimental support for this proposition8Suzuki H Hurihara Y Takeya M Kamada N Kataoka M Jishage K Ueda O Sakaguchi H Higashi T Suzuki T Takashima Y Kawabe Y Cynshi O Wada Y Honda M Kurihara H Aburatani H Doi T Matsumoto A Azuma S Noda T Toyoda Y Itakura H Yazaki Y Kodama T et al.A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection.Nature. 1997; 386: 292-296Crossref PubMed Scopus (1024) Google Scholar that was not discussed in the context of evolutionary biology. The study was motivated by a theory of atherogenesis that invokes a major role for arterial wall damage mediated by posttranslationally modified (particularly oxidized) low density lipoproteins.9Brown MS Goldstein JC Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis.Annu Rev Biochem. 1983; 52: 223-261Crossref PubMed Google Scholar, 10Aviram M Interaction of oxidized low density lipoprotein with macrophages in atherosclerosis, and the antiatherogenicity of antioxidants.Eur J Clin Chem Clin Biochem. 1996; 34: 599-608PubMed Google Scholar, 11Steinberg D Lewis A: Conner Memorial Lecture. Oxidative modification of LDL and atherogenesis.Circulation. 1997; 95: 1062-1071Crossref PubMed Scopus (706) Google Scholar These molecules are picked up by macrophages, the body's scavengers, via particular classes of promiscuous receptors (“molecular flypaper”),12Krieger M Acton S Ashkenas J Pearson A Penman M Resnick D Molecular flypaper, host defense, and atherosclerosis: structure, binding properties, and functions of macrophage scavenger receptors.J Biol Chem. 1993; 268: 4569-4572Abstract Full Text PDF PubMed Google Scholar the macrophage scavenger receptors. These macrophages are thought to be the major sources of the lipid-laden foam cells that appear in the early “fatty streak” stage of atherogenesis. Although rodents are notoriously resistant to spontaneous atherosclerosis, mice homozygous for null mutations at the apolipoprotein E locus develop marked hyperlipidemia and a form of progressive atherosclerosis; lipoprotein oxidation appears to play a role in the pathogenesis.13Palinski W Ord VA Plump AS Breslow JL Steinberg D Witztum JL ApoE-deficient mice are a model of lipoprotein oxidation in atherogenesis: demonstration of oxidation-specific epitopes in lesions and high titers of autoantibodies to malondialdehyde-lysine in serum.Arterioscler Thromb. 1994; 14: 605-616Crossref PubMed Scopus (474) Google Scholar Suzuki et al8Suzuki H Hurihara Y Takeya M Kamada N Kataoka M Jishage K Ueda O Sakaguchi H Higashi T Suzuki T Takashima Y Kawabe Y Cynshi O Wada Y Honda M Kurihara H Aburatani H Doi T Matsumoto A Azuma S Noda T Toyoda Y Itakura H Yazaki Y Kodama T et al.A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection.Nature. 1997; 386: 292-296Crossref PubMed Scopus (1024) Google Scholar crossed such mice with mice bearing targeted lesions in a macrophage scavenger receptor gene. Such doubly deficient mice were found to be significantly more resistant to atherosclerosis. Also of great interest was the finding that mice deficient in macrophage scavenger receptor function were highly susceptible to infection by a gram-positive bacterium, Listeria monocytogenes, and by the type 1 human herpesvirus. The relevant macrophage receptor had previously been shown to bind to a wide range of gram-positive bacteria, including streptococci, staphylococci, and enterococci14Dunne DW, Resnick D, Greenberg J, Krieger M, Joiner KA: The type I macrophage scavenger receptor binds to gram-positive bacteria and recognizes lipoteichoic acid. Proc Natl Acad Sci USA 1994, 1863–1867Google Scholar as well as to a form of bacterial endotoxin.15Ashkenas J Penman M Vasile E Acton S Freeman M Krieger M Structures and high and low affinity ligand binding properties of murine type I and type II macrophage scavenger receptors.J Lipid Res. 1993; 34: 983-1000Abstract Full Text PDF PubMed Google Scholar There is less information concerning the potential role of macrophage scavenger receptors in the defense against viral agents, but a role for nonparenchymal liver cells in the clearance of plasmids16Yoshida M Mahoat RI Kawabata K Takakura Y Hashida M Disposition characteristics of plasmid DNA in the single-pass rat liver perfusion system.Pharmaceutical Res. 1996; 13: 599-603Crossref PubMed Scopus (67) Google Scholar and the binding of certain classes of polynucleotides to macrophage scavenger receptors17Pearson AM Rich A Krieger M Polynucleotide binding to macrophage scavenger receptors depends on the formation of base- quartet-stabilized four-stranded helices.J Biol Chem. 1993; 268: 3546-3554Abstract Full Text PDF PubMed Google Scholar is consistent with such a role. The genomes of today's populations of Homo sapiens have been substantially shaped by the selective resistance to infectious disease of remote ancestors.18Ewald PW Evolution of Infectious Disease. Oxford University Press, New York1994Google Scholar Gene action at the macrophage scavenger receptor locus on chromosome 819Emi M Asaoka H Matsumoto A Itakura H Kurihara Y Wada Y Kanamori H Yazaki Y Takahashi E Lepert M et al.Structure, organization, and chromosomal mapping of the human macrophage scavenger receptor gene.J Biol Chem. 1993; 268: 2120-2125Abstract Full Text PDF PubMed Google Scholar has undoubtedly played an important role in this respect. Domains of that gene have ancient evolutionary origins20Freeman M Ashkenas J Rees DJ Kingsley DM Copeland NG Jenkins NA Krieger M An ancient, highly conserved family of cysteine-rich protein domains revealed by cloning type I and type II murine macrophage scavenger receptors.Proc Natl Acad Sci USA. 1990; 87: 8810-8814Crossref PubMed Scopus (262) Google Scholar and potential roles in the defenses of multicellular organisms against microbial pathogens and their toxins. Given our present diets and our relatively long life spans (which, of course, have also been molded by ancient selective forces),2Hamilton WD The moulding of senescence by natural selection.J Theor Biol. 1966; 12: 12-45Crossref PubMed Scopus (1489) Google Scholar we now appear to be paying a price for such reproductive phases of our life histories. This hypothesis predicts that mutations and polymorphisms at the macrophage scavenger locus on chromosome 8 will modulate individual susceptibility to atherogenesis.
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