title: Mechanisms of hypercholesterolemia and atherosclerosis.
abstract: Hypercholesterolemia is the result of an imbalance between two basic cholesterol homeostatic mechanisms. One is related to intercellular and the other to extracellular cholesterol homeostasis. The human organism gives always absolute priority to the intracellular homeostasis. The naturally occurring balance between both systems can be disturbed: 1) By genetic factors, one of them located on chromosome 19 and governing the number of LDL-receptors on the cell membrane (liver, arterial wall, adrenals, fibroblasts, etc.). Total genetic absence of malfunction of LDL-receptors is seen in homozygote familial hypercholesterolemia, with ischemic heart disease between ages 2 and 25. Less harmful situations arise from heterozygote familial hypercholesterolemia and from other genetic defects (among them those located at the gene of apo E on chromosome 19 and of apo AI on chromosome 11). 2) By nutritional factors decreasing or totally blocking the number of active LDL-receptors. This has been demonstrated in the rabbit, hamster, dog, baboon and humans. Overloading the organism with dietary cholesterol and saturated fat is one extremely common factor in western societies. Certain fats (omega-6 and omega-3 polyunsaturated, and oleic acid) may be beneficial. Other factors are generally of lesser importance. 3) By a combination in different proportions of 1) and 2). Severe dietary overloading with cholesterol and saturated fat in the rabbit results in early atherosclerotic lesions resembling almost totally those produced by the genetic absence of LDL-receptors (Watanabe rabbit). In humans from western countries the serum LDL-level is more related to environmental factors, whereas the HDL-level is more related to genetic factors. Age is an important factor integrating the effects of genetics and environmental deviations. The influence of sex is also important. Serum cholesterol in western countries is increasing markedly with age, but this growth of serum cholesterol with age is totally different between sexes. Serum cholesterol is on the average only equal in both sexes at ages 3, 10, 25 and 50. It is higher in males between ages 25 and 50 and higher in females between ages 3 to 10, 10 to 25 and above 50 years. In general females are less susceptible to higher cholesterolemia than males except at very old ages (above 80-85 years). Together with other observations of sex linked differences this points to the influence of a sex linked chromosome, most probably the X-chromosome. The susceptibility of females in a given population decreases with decreasing levels of infectious diseases, the opposite is true for males.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Epidemiology, K.U. Leuven, Belgium.
authors.forename: J V
authors.initials: JV
authors.lastname: Joossens
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology; D001696:Biomechanical Phenomena; D001777:Blood Coagulation; D001794:Blood Pressure; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood; D002875:Chromosomes; D004777:Environment; D005260:Female; D006706:Homeostasis; D006801:Humans; D006937:Hypercholesterolemia / Q000209:etiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics; D012907:Smoking; D013997:Time Factors
chemical_list: D002784:Cholesterol