Transforming growth factor-beta: the key to understanding lipoprotein(a)?
Most large studies of the blood parameters that act as risk factors for myocardial infarction, stroke and atherosclerosis have identified elevated circulating levels of lipoprotein(a) as an important risk factor. Lipoprotein(a) consists of an LDL particle that is covalently bound to the distinguishing protein component apolipoprotein(a). Ever since apolipoprotein(a) was cloned in 1987 and the marked sequence homology to plasminogen was noted, mechanisms for the atherogenic activity of lipoprotein(a), based on the competitive inhibition of plasminogen activity, have been proposed. However, with the availability of transgenic mice expressing both human apolipoprotein(a) and lipoprotein(a), recent studies have demonstrated that lipoprotein(a) acts to inhibit plasminogen activation in vivo. One consequence of this is reduced activation of the cytokine transforming growth factor-beta, an important regulator of vessel wall structure.
Grainger
D J
DJ
Department of Biochemistry, University of Cambridge, UK.
Metcalfe
J C
JC
D000818:Animals; D001054:Apolipoproteins A / Q000494:pharmacology; D001161:Arteriosclerosis / Q000209:etiology; D001808:Blood Vessels / Q000378:metabolism; D005260:Female; D006801:Humans; D017270:Lipoprotein(a) / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010958:Plasminogen / Q000378:metabolism; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000502:physiology*
D001054:Apolipoproteins A; D017270:Lipoprotein(a); D016212:Transforming Growth Factor beta; D010958:Plasminogen