Use of Apolipoprotein Parameters and Endpoints in Drug Development and Approval Processes
1998; Elsevier BV; Volume: 81; Issue: 8 Linguagem: Inglês
10.1016/s0002-9149(98)00260-4
ISSN1879-1913
Autores Tópico(s)Lipoproteins and Cardiovascular Health
ResumoPlasma lipoproteins are particles containing lipid and protein moieties. The major constituents of lipid moieties include cholesterol, cholesteryl esters, triglycerides, and phospholipids. Protein moieties include proteins referred to as apolipoproteins (apo) AI, A-II, A-IV, B-100, C-I, C-II, C-III, D, E, F, G, I, and J. 1. Alaupovic P. The significance of apolipoproteins for structure, function and classification of plasma lipoproteins. in: Bradley W.A. Gianturco S.H. Segrest J.P. Methods in Enzymology. Plasma Lipoproteins, Part C, Quantitation. Academic Press, San Diego1996: 32-60 Crossref Google Scholar It is now generally accepted that apolipoproteins play essential roles in maintaining the structural integrity and functional specificity of plasma lipoproteins. 1. Alaupovic P. The significance of apolipoproteins for structure, function and classification of plasma lipoproteins. in: Bradley W.A. Gianturco S.H. Segrest J.P. Methods in Enzymology. Plasma Lipoproteins, Part C, Quantitation. Academic Press, San Diego1996: 32-60 Crossref Google Scholar , 2. Francheschini G. Apolipoprotein function in health and disease insights from natural mutations. Eur J Clin Invest. 1996; 26: 733-746 Crossref PubMed Scopus (29) Google Scholar , 3. Patsch W. Gotto Jr, A.M. Apolipoproteins pathophysiology and clinical implications. in: Bradley W.A. Gianturco S.H. Segrest J.P. Methods in Enzymology Plasma Lipoproteins. Part C, Quantitation. Academic Press, San Diego1996: 3-32 Crossref Google Scholar Apolipoproteins are directly involved in metabolic conversions of different lipoprotein classes including secretion, prevention of premature removal from the circulation, recognition of binding and removal sites on cellular surfaces, and activation of lipolytic enzymes. Because of these properties, apolipoprotein concentrations may be used as valuable clues for identifying normal and impaired processes of lipid transport. 3. Patsch W. Gotto Jr, A.M. Apolipoproteins pathophysiology and clinical implications. in: Bradley W.A. Gianturco S.H. Segrest J.P. Methods in Enzymology Plasma Lipoproteins. Part C, Quantitation. Academic Press, San Diego1996: 3-32 Crossref Google Scholar , 4. Alaupovic P. McConathy W.J. Fesmire J. Tavella M. Bard J.M. Profiles of apolipoproteins and apolipoprotein B-containing lipoprotein particles in dyslipoproteinemias. Clin Chem. 1988; 34: B13-B27 PubMed Google Scholar , 5. Bachorik P.S. Kwiterovich Jr, P.O. Apolipoprotein measurements in clinical biochemistry and their utility vis-a-vis conventional assays. Clin Chim Acta. 1988; 178: 1-34 Crossref PubMed Scopus (32) Google Scholar , 6. Albers J.J. Brunzell J.D. Knopp R.H. Apoprotein measurements and their clinical application. Clin Lab Med. 1989; 9: 137-152 PubMed Google Scholar However, despite the undisputed significance of apolipoproteins for the formation and lipid-transport capacity of lipoproteins, the pathophysiologic processes of lipid transport and corresponding interventions have usually been characterized, defined, and monitored by lipid, not apolipoprotein, concentrations. This attitude has resulted from various factors: historical development of the field, conceptual views about lipid transport and atherogenesis, and methodologic considerations. Thus, the National Cholesterol Education Program (NCEP) has provided recommendations for the desirable concentrations and reliable measurement of lipids, but not apolipoproteins. 7. Report of the National Cholesterol Education Program Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults. Arch Intern Med. 1988; 148: 36-39 Crossref PubMed Scopus (2130) Google Scholar , 8. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel II). JAMA. 1993; 268: 3015-3023 Google Scholar
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