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Lipoprotein(a) : new insights into an atherogenic lipoprotein

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Abstract

Lipoprotein(a) constitutes a macromolecular complex in human plasma that combines structural features from the blood clotting and the lipoprotein systems. Aside from the discovery of lipoprotein(a) [Lp(a)] as a potential independent risk factor for premature cardiovascular disease its physiological role and activity remains obscure. Since the site of catabolism has not yet been fully characterized, there is intensive search for factors which influence plasma Lp(a) levels. Several clinical conditions and metabolic states have been identified to be added to the disorders of the lipid metabolism itself that modulate Lp(a) plasma levels. Diseases of the kidney and their accompanying factors (proteinuria and nephrotic syndrome) as well as end-stage renal disease and their treatment modalities (hemodialysis, peritoneal dialysis, and kidney transplantation) have all been found to increase Lp(a) plasma levels substantially. Fluctuations in Lp(a) also seem to occur in states of hormonal changes, such as in diabetes mellitus, after estrogen treatment, and during pregnancy. Recently a plausible mechanism for the atherogenic activity of Lp(a) has been ascribed to the inhibiting effect of Lp(a) on plasminogen activation, thus decreasing plasmin formation which in turn reduces the activation of transforming growth factor β, a potent inhibitor of smooth muscle cell proliferation. Lp(a) exerts its pathological effect at plasma levels in the range of 20–30 mg/dl. Therefore, it seems mandatory to quantitate Lp(a) levels in patients who are at risk of developing progressive atherosclerotic disease to identify those with high levels of this unique atherogenic lipoprotein. Since plasma levels of Lp(a) are insensitive to diet, exercise, and most lipid-lowering drugs, the reduction of other risk factors that predispose to atherosclerotic disease is the only clinical strategy at present.

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Abbreviations

apo(a):

apolipoprotein(a)

apoB:

apolipoprotein B

CAPD:

continuous ambulatory peritoneal dialysis

ESRD:

end-stage renal disease

FCHL:

familial combined hyperlipidemia

FH:

familial hypercholesterolemia

HD:

hemodialysis

HGF:

hepatocyte growth factor

HMG-CoA:

3-hydroxy-3-methyl glutaryl coenzyme A

LDL:

low-density lipoprotein

Lp(a):

lipoprotein(a)

TGF-R:

transforming growth factor-β

TGRLP:

triglyceride-rich lipoproteins

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  1. Abteilung Innere Medizin IV, Medizinische Universitätsklinik, Hugstetterstrasse 55, D-79106, Freiburg, Germany

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Bartens, W., Wanner, C. Lipoprotein(a) : new insights into an atherogenic lipoprotein. Clin Investig 72, 558–567 (1994). https://doi.org/10.1007/BF00227446

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