Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipoprotein(a) (Lp[a]) is a low density lipoprotein particle that contains plasminogen-like apolipoprotein(a). Recent studies suggest an association of Lp(a) with atherosclerotic vascular disease. We have studied the accumulation of Lp(a) in atherosclerotic arteries of monkeys with diet-induced atherosclerosis. Immunohistochemistry with monospecific Lp(a) antisera revealed striking accumulations of Lp(a) in atherosclerotic coronary artery lesions. There was no Lp(a) in the normal, nonatherosclerotic arteries. Analysis of paired tissue and serum samples from 17 male hyperlipoproteinemic monkeys revealed a significant correlation between aortic wall Lp(a) and serum Lp(a) levels. The serum cholesterol level failed to correlate with either aortic Lp(a) or serum Lp(a). These results add further evidence for the potential role of Lp(a) in the pathogenesis of atherosclerosis.
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PMID:Lipoprotein(a) in diet-induced atherosclerosis in nonhuman primates. 182 15

Although the mechanism by which lipoprotein(a) [Lp(a)] contributes to vascular disease remains unclear, consequences of its binding to the vessel surface are commonly cited in postulated atherogenic pathways. Because of the presence of plasminogen-like lysine binding sites (LBS) in apo(a), fibrin binding has been proposed to play an important role in Lp(a)'s vascular accumulation. Indeed, LBS are known to facilitate Lp(a) fibrin binding in vitro. To examine the importance of apo(a) LBS in Lp(a) vascular accumulation in vivo, we generated three different apo(a) cDNAs: (a) mini apo(a), based on wild-type human apo(a); (b) mini apo(a) containing a naturally occurring LBS defect associated with a point mutation in kringle 4-10; and (c) human- rhesus monkey chimeric mini apo(a), which contains the same LBS defect in the context of several additional changes. Recombinant adenovirus vectors were constructed with the various apo(a) cDNAs and injected into human apoB transgenic mice. At the viral dosage used in these experiments, all three forms of apo(a) were found exclusively within the lipoprotein fractions, and peak Lp(a) plasma levels were nearly identical (approximately 45 mg/dl). In vitro analysis of Lp(a) isolated from the various groups of mice confirmed that putative LBS defective apo(a) yielded Lp(a) unable to bind lysine-Sepharose. Quantitation of in vivo Lp(a) vascular accumulation in mice treated with the various adenovirus vectors revealed significantly less accumulation of both types of LBS defective Lp(a), relative to wild-type Lp(a). These results indicate a correlation between lysine binding properties of Lp(a) and vascular accumulation, supporting the postulated role of apo(a) LBS in this potentially atherogenic characteristic of Lp(a).
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PMID:Lipoprotein(a) vascular accumulation in mice. In vivo analysis of the role of lysine binding sites using recombinant adenovirus. 929 16

Lipoprotein(a) [Lp(a)], an LDL-like lipoprotein, has an additional carrier protein - apo (a), which closely resembles plasminogen. Epidemiological and experimental studies provide overwhelming evidence that Lp(a) may promote atherogenesis and thrombosis via its LDL-like and plasminogen-like mechanisms. With more than 90% variance explainable by the apo(a) gene, Lp(a) is detectable at birth and increases with age until adolescence when the Lp(a) reaches adult levels. There is a striking close offspring-parental correlation in Lp(a) levels, which is present at birth and tracks for life. While Lp(a) levels are highly regulated genetically and difficult to change, it appears that factors during the first year of life may have more impact on Lp(a) expression profiles, which possibly have long-lasting effects. Lp(a) levels are elevated in children with obesity, diabetes, renal diseases, hypercholesterolemia and are predictive of vascular diseases in themselves and other family members. We suggest that Lp(a) should be routinely measured in both children and adults for vascular disease risk factor assessment, at least among those with high conventional Coronary Artery Disease (CAD) risk factors and those with established CAD.
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PMID:Lipoprotein(a) in children and adolescence. 1643 16