2.P.165 Lipoprotein(a) is a potent chemoattractant selective for human peripheral monocytes

Syrovets, Tatiana; Thillet, Joëlle; Chapman, M. John; Simmet, Th.

doi:10.1016/s0021-9150(97)88803-x

Cited by 19 publications

(19 citation statements)

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“…A thioglycollate inflammation model was used in which mice (n = 7 per group) were injected intraperitoneally with 0. (28), or in its suppression of plasminogen activation, which blunts matrix degradation and the generation of chemoattractants, including fibrin derivatives (50,51) and plasmin, itself (52). With normal plasma levels of Plg, we found that plasma from pCPB-deficient mice supported only a modest increase in fibrinolysis compared with plasma from wild-type animals in vitro.…”

Section: Figurementioning

confidence: 73%

In vivo regulation of plasminogen function by plasma carboxypeptidase B

Swaisgood

Schmitt²,

Eaton³

et al. 2002

J. Clin. Invest.

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The major functions of plasminogen (Plg) in fibrinolysis and cell migration depend on its binding to carboxy-terminal lysyl residues. The ability of plasma carboxypeptidase B (pCPB) to remove these residues suggests that it may act as a suppressor of these Plg functions. To evaluate this role of pCPB in vivo, homozygote pCPB-deficient mice were generated by homologous recombination, and the resulting pCPB–/– mice, which were viable and healthy, were mated to Plg–/– mice. Plg+/– mice show intermediate levels of fibrinolysis and cell migration compared with Plg wild-type and deficient mice, reflecting the intermediate levels of the Plg antigen in their plasma. Differences in Plg-dependent functions between pCPB+/+, pCPB+/–, and pCPB–/– mice were then analyzed in a Plg+/– background. In a pulmonary clot lysis model, fibrinolysis was significantly increased in mice with partial (pCPB+/–) or total absence (pCPB–/–) of pCPB compared with their wild-type counterparts (pCPB+/+). In a thioglycollate model of peritoneal inflammation, leukocyte migration at 72 hours increased significantly in Plg+/–/pCPB+/– and Plg+/–/pCPB–/– compared with their wild-type counterparts. These studies demonstrate a definitive role of pCPB as a modulator of the pivotal functions of Plg in fibrinolysis and cell migration in vivo

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Section: Figurementioning

confidence: 73%

In vivo regulation of plasminogen function by plasma carboxypeptidase B

Swaisgood

Schmitt²,

Eaton³

et al. 2002

J. Clin. Invest.

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“…Lp(a) is unique in its potential to be involved via either one or both of these pathways. Lp(a) could interfere with plasminogen activation (8) or platelet function (9), or it could contribute to inflammation (10) or endothelial dysfunction (11). Nevertheless, the lack of association in some populations has led to controversy regarding the use of Lp(a) as a marker of risk in common clinical practice.…”

Section: Elevated Plasma Concentrations Of Lipoprotein(a) [Lp(a)]mentioning

confidence: 99%

Determination of lipoprotein(a) kringle repeat number from genomic DNA: copy number variation genotyping using qPCR

Lanktree

Rajakumar

Brunt

et al. 2009

Journal of Lipid Research

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Plasma lipoprotein(a) [Lp(a)] concentration is related to risk of cardiovascular disease. The defining protein component of Lp(a) particles, apolipoprotein(a) [apo(a)], is encoded by the LPA gene. Apo(a) is extremely heterogeneous in size due to a common copy number variation, leading to a variable number of kringle-IV type 2 (KIV2)-like domains. Alleles with fewer KIV2 repeats, encoding smaller apo(a) isoforms, are associated with higher plasma Lp(a) concentrations. Two principal methods to detect variation in KIV2 repeat number are electrophoresis with immunoblotting to detect apo(a) protein isoforms or pulse-field electrophoresis of unamplified genomic DNA to detect the variation of the LPA gene. Both methods are technically challenging, laborious, and time consuming. Here, we report a rapid method to determine the number of KIV2 repeats in LPA from genomic DNA using quantitative real-time polymerase chain reaction (qPCR). With qPCR, we found KIV2 repeat number was correlated with both apo(a) isoform size as determined by immunoblotting (r s 5 0.50, P , 1 3 10 26 ) and with plasma Lp(a) concentration (r s 5 0.30, P , 1 3 10 26 ). The qPCR technique permits rapid evaluation of apo(a) size from genomic DNA, and thus would provide an adjunctive genomic variable, in addition to LPA single nucleotide polymorphisms, for evaluating the genetic determinants of plasma Lp(a) concentration in genetic epidemiology studies of cardiovascular disease outcomes.-Lanktree, M. B., C. Rajakumar, J. H. Brunt, M. L. Koschinsky, P. W. Connelly, and R. A. Hegele. Determination of lipoprotein(a) kringle repeat number from genomic DNA: copy number variation genotyping using qPCR. J. Lipid Res.

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“…37 Two recent studies demonstrated that Lp(a) induces chemotactic activity to human monocytes in a dosedependent fashion. 38,39 Lp(a) enhances the expression of intercellular adhesion molecule-1. 40 Because Lp(a) accumulates in the subendothelial space of the vessel wall, it may act This analysis focused on subjects with preexisting atherosclerosis (nϭ326).…”

Section: Kronenberg Et Al Lp(a) Apo(a) Phenotype and Atherogenesismentioning

confidence: 99%

Role of Lipoprotein(a) and Apolipoprotein(a) Phenotype in Atherogenesis

et al. 1999

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Background-Experimental studies have suggested both atherogenic and thrombogenic properties of lipoprotein (a) [Lp(a)], depending on Lp(a) plasma concentrations and varying antifibrinolytic capacity of apolipoprotein(a) [apo(a)] isoforms. Epidemiological studies may contribute to assessment of the relevance of these findings in the general population. Methods and Results-This study prospectively investigated the association between Lp(a) plasma concentrations, apo (a) phenotypes, and the 5-year progression of carotid atherosclerosis assessed by high-resolution duplex ultrasound in a random sample population of 826 individuals. We differentiated early atherogenesis (incident nonstenotic atherosclerosis) from advanced (stenotic) stages in atherosclerosis that originate mainly from atherothrombotic mechanisms. Lp(a) plasma concentrations predicted the risk of early atherogenesis in a dose-dependent fashion, with this association being confined to subjects with LDL cholesterol levels above the population median (3.3 mmol/L). Apo(a) phenotypes were distributed similarly in subjects with and without early carotid atherosclerosis. In contrast, apo(a) phenotypes of low molecular weight emerged as one of the strongest risk predictors of advanced stenotic atherosclerosis, especially when associated with high Lp(a) plasma concentrations (odds ratio, 6.4; 95% CI, 2.8 to 14.9). Conclusions-Lp(a) is one of the few risk factors capable of promoting both early and advanced stages of atherogenesis.Lp(a) plasma concentrations predicted the risk of early atherogenesis synergistically with high LDL cholesterol. Low-molecular-weight apo(a) phenotypes with a putatively high antifibrinolytic capacity in turn emerged as one of the leading risk conditions of advanced stenotic stages of atherosclerosis.

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2.P.165 Lipoprotein(a) is a potent chemoattractant selective for human peripheral monocytes

Cited by 19 publications

References 0 publications

In vivo regulation of plasminogen function by plasma carboxypeptidase B

In vivo regulation of plasminogen function by plasma carboxypeptidase B

Determination of lipoprotein(a) kringle repeat number from genomic DNA: copy number variation genotyping using qPCR

Role of Lipoprotein(a) and Apolipoprotein(a) Phenotype in Atherogenesis

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