Lipoprotein(a), a variant of LDL carrying the adhesive glycoprotein apo(a), is a leading risk factor for cardiovascular disease. Lipoprotein(a) (Lp(a)) is found in humans and subhuman primates but rarely in lower mammals. Better understanding of the evolutionary advantage of this molecule should elucidate its physiological role. We developed a new mouse model with two characteristics of human metabolism: the expression of Lp(a) and the lack of endogenous ascorbate (vitamin C) production. We show that dietary deficiency of ascorbate increases serum levels of Lp(a). Moreover, chronic hypoascorbemia and complete depletion of ascorbate (scurvy) leads to Lp(a) accumulation in the vascular wall and parallels atherosclerotic lesion development. The results suggest that dietary ascorbate deficiency is a risk factor for atherosclerosis independent of dietary lipids. We provide support for the concept that Lp(a) functions as a mobile repair molecule compensating for the structural impairment of the vascular wall, a morphological hallmark of hypoascorbemia and scurvy.
Keywords: Gulo-/-; Lipoprotein(a); Lp(a); Lp(a) transgene; atherosclerosis; cvd risk factors; hypoascorbemia; vascular plaques; vitamin C.