Apolipoprotein(a) Attenuates Endogenous Fibrinolysis in the Rabbit Jugular Vein Thrombosis Model In Vivo

Biemond, Bart J.; Friederich, Philip W.; Koschinsky, Marlys L.; Levi, Marcel; Sangrar, Waheed; Xia, Jiazhi; Büller, Harry R.; Cate, J. W. Ten

doi:10.1161/01.cir.96.5.1612

Cited by 52 publications

(30 citation statements)

References 29 publications

(13 reference statements)

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“…In addition, apo(a) was not able to influence the activity of plasmin itself in degrading fibrin (46). These findings are supported by studies of thrombolysis in rabbit jugular vein (50) and transgenic mice expressing apo(a) (51). In addition, induction of carotid of mural thrombi or through effects in the vascular wall, such as extracellular matrix breakdown, cell migration, and angiogenesis (43).…”

Section: Interference With Functions Of Plasminogenmentioning

confidence: 85%

Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease?

Boffa

Koschinsky

2016

Journal of Lipid Research

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Section: Interference With Functions Of Plasminogenmentioning

confidence: 85%

Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease?

Boffa

Koschinsky

2016

Journal of Lipid Research

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204

125

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“…8 For example, several studies have suggested that Lp(a) can interfere with plasminogen activation by competing for binding to fibrin and consequently attenuate fibrinolysis. 9,10 Lp(a) may also promote thrombosis by a mechanism independent of plasminogen. 11 Apo(a) size, kringle repeat number, and Lp(a) plasma levels are all associated with CHD.…”

mentioning

confidence: 99%

Genetic Variants in the Apolipoprotein(a) Gene and Coronary Heart Disease

Luke

Shiffman

et al. 2011

Circ Cardiovasc Genet

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T wo independent single-nucleotide polymorphisms (SNPs) in the gene encoding apolipoprotein(a) (LPA) have been shown to be associated with coronary heart disease (CHD) and lipoprotein(a) levels in Caucasians. For the missense SNP rs3798220 (Ile4399Met), carriers of 1 or 2 copies of the minor allele (Met) were at 57% increased risk of CHD. For the intronic SNP rs10455872, the risk of CHD increased by 42% for each copy of the minor allele. The rs3798220 SNP was also associated with differential response to aspirin therapy in the Women's Health Study; carriers of the minor allele had a significant reduction in CHD events from aspirin therapy, whereas noncarriers did not have a significant reduction.Lipoprotein(a) [Lp(a)] is a lipoprotein particle that consists of an apolipoprotein(a) [apo(a)] molecule covalently linked by a disulfide bond to the apolipoprotein B-100 (apoB-100) component of a low-density lipoprotein (LDL)-like particle (Figure 1, modified on the Albers et al 1 figure). The LPA gene, which encodes apo(a), is thought to have been generated by a duplication of the neighboring plasminogen gene. 2 Like the plasminogen protein, the apo(a) has a protease-like domain and multiple kringle domains. Different variants of the LPA gene can affect the plasma level of Lp(a), encode apo(a) size variants (ie, kringle repeat length variations), or both.Lp(a) may contribute to cardiovascular disease through complex mechanisms that involve proatherogenic and prothrombotic pathways. 3,4 Lp(a) accumulates in the arterial wall of patients with coronary heart disease (CHD) 5 and contributes to cholesterol deposition, induction of endothelial adhesion molecules, chemotaxis of monocytes, foam cell formation, and also to smooth muscle cell proliferation and dedifferentiation. 6 Lp(a) binds oxidized phospholipids that are capable of modulating inflammation and progression of atherosclerosis. 7 In addition, the structural homology between apo(a) and plasminogen suggests that Lp(a) promotes thrombosis. 8 For example, several studies have suggested that Lp(a) can interfere with plasminogen activation by competing for binding to fibrin and consequently attenuate fibrinolysis. 9,10 Lp(a) may also promote thrombosis by a mechanism independent of plasminogen. 11Apo(a) size, kringle repeat number, and Lp(a) plasma levels are all associated with CHD. [12][13][14] For example, depending on the gene variant, the LPA gene can encode apo(a) that contains from 3 to Ͼ40 kringle IV type 2 (KIV-2) repeats, and the risk of CHD or stroke was 2-fold higher among individuals having small apo(a) molecules (Յ22 KIV-2 repeats) compared with those having larger apo(a) molecules (Ͼ22 repeats) in a recent meta-analysis of 40 studies involving Ͼ11 000 patients and Ͼ46 000 control subjects. 15 Elevated Lp(a) plasma levels are also a risk factor for CHD: a recent meta-analysis of 36 prospective studies involving Ͼ126 000 individuals found "continuous, independent, and modest associations of Lp(a) concentration with risk of CHD and stroke." 16 Howeve...

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“…The molecular structure of Lp(a) is similar to that of plasminogen, so potentially it can reduce fibrinolysis by inhibiting the plasmin production, which may thus promote the formation of thrombi. 33 Lp(a) reduces the activation of transforming growth factor-(an inhibitor of cellular migration), thereby inducing the conveyance and proliferation of smooth muscle cells. 34 Lp(a) binds to the extracellar matrix and is ingested by macrophages, resulting in their accumulation of lipid and thus promoting arteriosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Association Between Plasma Lipoprotein(a) Concentration and Restenosis After Stent Implantation

Kamitani

Taniguchi

Miyai

et al. 2005

Circ J

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Background The plasma concentration of lipoprotein (a) [Lp(a)] is associated with atherosclerotic and thrombotic vascular diseases. The aim of the present study was to evaluate the association between plasma Lp(a) concentration and in-stent restenosis. Methods and ResultsOne hundred and 9 patients with successful elective coronary stent implantation underwent follow-up angiography at 24±6 weeks. Restenosis after stent implantation occurred in 38 patients. Univariate analysis showed that the reference diameter of the lesion was smaller in the restenosis group (2.93±0.29 mm) than in the no-restenosis group (3.21±0.43 mm) (p<0.05). The lesion was longer in the restenosis group (14.2± 5.3 mm) than in the no-restenosis group (11.6±4.9 mm) (p<0.05). Plasma Lp(a) concentrations in the restenosis group (30.5±23.9 mg/dl) were higher than in the no-restenosis group (16.9±11.1 mg/dl) (p<0.01). Other lipid concentrations were similar in both groups. Among the plasma Lp(a) concentrations, the rate of restenosis (71.4%) in the high Lp(a) group (>40 mg/dl) (n=14) was greater compared with the other groups: 33.3% in the intermediate Lp(a) group (10-40 mg/dl) (n=54), and 24.4% in the low Lp(a) group (<10 mg/dl) (n=41) (p<0.01). The late loss (0.57±0.53 mm) in the low Lp(a) group was significantly less than the other groups: 0.88±0.47 mm in the intermediate Lp(a) group, and 1.08±0.56 mm in the high Lp(a) group (p<0.05). In a multivariate regression model, plasma Lp(a) concentration remained significant as an independent predictor of restenosis in patients undergoing stent implantation (p=0.020 odds ratio (OR) 1.37 95%conficence interval (CI) 1.050-1.793), although the reference diameter (p=0.025 OR 0.23 95%CI 0.061-0.830) and lesion length (p=0.021 OR 1.12 95%CI 1.017-1.232) were related to stent restenosis. Conclusions Plasma Lp(a) concentration is an independent predictor of stent restenosis. (Circ J 2005; 69: 644 -649)

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Apolipoprotein(a) Attenuates Endogenous Fibrinolysis in the Rabbit Jugular Vein Thrombosis Model In Vivo

Cited by 52 publications

References 29 publications

Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease?

Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease?

Genetic Variants in the Apolipoprotein(a) Gene and Coronary Heart Disease

Association Between Plasma Lipoprotein(a) Concentration and Restenosis After Stent Implantation

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