Cha John, Niedzwiecki Aleksandra, Rath Matthias
Dr. Rath Research Institute Santa Clara, CA, USA.
Am J Cardiovasc Dis. 2015 Mar 20;5(1):53-62. eCollection 2015.
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.
脂蛋白(a)是低密度脂蛋白的一种变体，携带黏附性糖蛋白载脂蛋白(a)，是心血管疾病的主要危险因素。脂蛋白(a)（Lp(a)）存在于人类和灵长类动物中，但在低等哺乳动物中很少见。更好地理解这种分子的进化优势应该能够阐明其生理作用。我们开发了一种具有人类代谢两个特征的新型小鼠模型：Lp(a)的表达和内源性抗坏血酸（维生素C）生成的缺乏。我们发现，饮食中缺乏抗坏血酸会增加血清Lp(a)水平。此外，慢性低抗坏血酸血症和抗坏血酸完全耗尽（坏血病）会导致Lp(a)在血管壁中积累，并与动脉粥样硬化病变发展平行。结果表明，饮食中缺乏抗坏血酸是独立于饮食脂质的动脉粥样硬化危险因素。我们支持这样的观点，即Lp(a)作为一种移动修复分子发挥作用，补偿血管壁的结构损伤，这是低抗坏血酸血症和坏血病的形态学特征。
