Renovascular arteriovenous differences in Lp[a] plasma concentrations suggest removal of Lp[a] from the renal circulation

Kronenberg, Florian; Trenkwalder, Evi; Lingenhel, Arno; Friedrich, Guy; Lhotta, Karl; Schober, Maria; Moes, N.; König, Paul; Utermann, Gerd; Dieplinger, Hans

doi:10.1016/s0022-2275(20)37150-9

Cited by 95 publications

(14 citation statements)

References 35 publications

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“…Our turnover study is one further important step in understanding Lp(a) catabolism and in line with previous studies suggesting the kidney to be involved in the metabolism of Lp(a). Kronenberg et al 19 measured Lp(a) levels in the ascending aorta and renal vein in 100 patients with normal kidney function. Lp(a) levels differed significantly between the two blood vessels with lower values in the venous samples.…”

Section: Discussionmentioning

confidence: 99%

“…Lp(a) levels differed significantly between the two blood vessels with lower values in the venous samples. 19 The authors suggested a removal of Lp(a) from the renal circulation and assigned the kidney a potentially active role in the catabolism of Lp(a). Oida et al 20 showed that urinary Lp(a) excretion correlates positively with kidney function, although the mechanisms involved were unclear.…”

Section: Discussionmentioning

confidence: 99%

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In vivo turnover study demonstrates diminished clearance of lipoprotein(a) in hemodialysis patients

Frischmann

Kronenberg

Trenkwalder

et al. 2007

Kidney International

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Lipoprotein(a) (Lp(a)) consists of a low-density lipoprotein-like particle and a covalently linked highly glycosylated protein, called apolipoprotein(a) (apo(a)). Lp(a) derives from the liver but its catabolism is still poorly understood. Plasma concentrations of this highly atherogenic lipoprotein are elevated in hemodialysis (HD) patients, suggesting the kidney to be involved in Lp(a) catabolism. We therefore compared the in vivo turnover rates of both protein components from Lp(a) (i.e. apo(a) and apoB) determined by stable-isotope technology in seven HD patients with those of nine healthy controls. The fractional catabolic rate (FCR) of Lp(a)-apo(a) was significantly lower in HD patients compared with controls (0.164+/-0.114 vs 0.246+/-0.067 days(-1), P=0.042). The same was true for the FCR of Lp(a)-apoB (0.129+/-0.097 vs 0.299+/-0.142 days(-1), P=0.005). This resulted in a much longer residence time of 8.9 days for Lp(a)-apo(a) and 12.9 days for Lp(a)-apoB in HD patients compared with controls (4.4 and 3.9 days, respectively). The production rates of apo(a) and apoB from Lp(a) did not differ significantly between patients and controls and were even lower for patients when compared with controls with similar Lp(a) plasma concentrations. This in vivo turnover study is a further crucial step in understanding the mechanism of Lp(a) catabolism: the loss of renal function in HD patients causes elevated Lp(a) plasma levels because of decreased clearance but not increased production of Lp(a). The prolonged retention time of Lp(a) in HD patients might importantly contribute to the high risk of atherosclerosis in these patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

In vivo turnover study demonstrates diminished clearance of lipoprotein(a) in hemodialysis patients

Frischmann

Kronenberg

Trenkwalder

et al. 2007

Kidney International

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“…This possibility was partly ruled out as the apo[a] mRNA levels in the liver, the major site of apo[a] production in transgenic rabbits, were similar in WHHL and normal transgenic rabbits. (40); therefore, we also investigated renal functions in WHHL rabbits. Biochemical analysis of rabbit plasma (BUN and creatine) and pathological studies on renal histology did not reveal any abnormalities in WHHL kidneys (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…6), suggesting that elevated hepatic synthesis of apo[a] did not account for the accumulation of Lp[a] in WHHL rabbits. Recent studies from other laboratories suggest that the kidney may be an alternative organ for apo[a] catabolism (40). Accordingly, we also investigated apo[a] expression in the kidney.…”

Section: Apo[a] Mrna Expressionmentioning

confidence: 99%

Defects of the LDL receptor in WHHL transgenic rabbits lead to a marked accumulation of plasma lipoprotein[a]

Fan

Challah

Shimoyamada

et al. 2000

Journal of Lipid Research

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In this study, we created LDL receptor (LDLr) defective (WHHL) transgenic rabbits expressing human apo[a] to examine whether LDLr mediates the Lp[a] clearance from the plasma. By crossbreeding WHHL rabbits with human apo[a] transgenic rabbits, we obtained two groups of human apo[a] transgenic rabbits with defective LDLr functions: apo[a] ؉ /0 WHHL heterozygous (LDLr ؉ / ؊ ) and apo[a] ؉ /0 WHHL homozygous (LDLr ؊ / ؊ ) rabbits. The lipid and lipoprotein levels of human apo[a] WHHL rabbits were compared to those of human apo[a] transgenic rabbits with normal LDLr functions (LDLr ؉ / ؉ ). The apo[a] production rate was evaluated by analyzing apo[a] mRNA expression in the liver, the major site for apo[a] synthesis in transgenic rabbits. We found that pre-␤ lipoproteins were markedly increased accompanied by a 2-fold increase in the plasma Lp[a] in apo[a] ؉ /0 /LDLr ؉ / ؊ rabbits and a 4.2-fold increase in apo[a] ؉ /0 /LDLr ؊ / ؊ rabbits compared with that in apo[a] ؉ /0 rabbits with normal LDLr function. In apo[a] ؉ /0 /LDLr ؊ / ؊ rabbits, there was a marked increase in plasma total cholesterol and triglycerides, as was found in their counterpart non-transgenic WHHL rabbits. Northern blot analysis revealed that hepatic apo[a] expression in WHHL transgenic rabbits was similar to that in LDLr ؉ / ؉ transgenic rabbits, suggesting the accumulation of plasma Lp[a] in WHHL transgenic rabbits was not due to increased apo[a] synthesis. In conclusion, absence of a functional LDLr leads to a marked accumulation of plasma Lp[a] in human apo[a] transgenic WHHL rabbits and LDLr may participate in the catabolism of Lp[a] in rabbits.-Fan, J., M. Challah, H. Shimoyamada, M. Shiomi, S. Marcovina, and T. Watanabe. Defects of the LDL receptor in WHHL transgenic rabbits lead to a marked accumulation of plasma lipoprotein[a].

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“…Second, after kidney transplantation in patients with impaired renal function, Lp(a) concentrations generally decrease. 4 Th ird, Kronenberg and co-workers 5 reported that Lp(a) levels in the renal vein are lower than those in the ascending aorta, suggesting that Lp(a) is removed in the renal circulation. Fourth, Reblin and co-workers 6 showed, in a heterologous rat model, that when Lp(a) is injected in rats, Lp(a) accumulates in the kidney tubules and apo(a) fragments are excreted in the urine.…”

mentioning

confidence: 99%

Evidence mounts for a role of the kidney in lipoprotein(a) catabolism

Albers

Koschinsky

Marcovina

2007

Kidney International

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Numerous studies have suggested a role of the kidney in lipoprotein(a) (Lp(a)) catabolism, but direct evidence is still lacking. Frischmann et al. demonstrate that the marked elevation of Lp(a) observed in hemodialysis patients results from a decrease in Lp(a) clearance rather than an increase in Lp(a) production, consistent with the notion that the kidney degrades Lp(a). More studies are needed to prove the biological relevance.

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Renovascular arteriovenous differences in Lp[a] plasma concentrations suggest removal of Lp[a] from the renal circulation

Cited by 95 publications

References 35 publications

In vivo turnover study demonstrates diminished clearance of lipoprotein(a) in hemodialysis patients

In vivo turnover study demonstrates diminished clearance of lipoprotein(a) in hemodialysis patients

Defects of the LDL receptor in WHHL transgenic rabbits lead to a marked accumulation of plasma lipoprotein[a]

Evidence mounts for a role of the kidney in lipoprotein(a) catabolism

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