Lipoprotein(a) and proliferative diabetic retinopathy in Type II diabetes mellitus: A role for isoforms with low molecular weight

Apolipoprotein(a) [apo(a)] displays a remarkable genetic heterogeneity of which the physiopathologic mechanisms are yet unknown. Its homology with plasminogen also suggests a pro-thrombotic role. To investigate whether or not lipoprotein(a) [Lp(a)] concentration and/or apo(a) isoforms correlate with the severity of diabetic retinopathy (DR), 113 Type II diabetic patients were studied. By fluorescein angiography, 3 classes of DR were considered: 'null' (40 subjects), 'non-proliferative' (37 subjects) and 'proliferative' (36 subjects). Apo(a) isoforms were detected by a capillary Western Blotting technique, resulting in the identification of 21 apo(a) isoforms with molecular weight (MW) varying from 400 to 775 kDa. Lp(a) plasma concentration did not correlate with the degree of DR (15.6 mg/dl in 'null', 17.8 mg/dl in 'non-proliferative' and 20.6 mg/dl in 'proliferative' DR group, p = 0.399). On the contrary, in subjects with proliferative DR there was a significant prevalence (65%) of low MW apo(a) isoforms (cut-off between 640 and 655 kDa), as compared to null DR (26%, p <0.01) and to non-proliferative DR (35%, p <0.05). In conclusion, low MW apo(a) isoforms could represent another possible biological marker of the genetic risk for the development and progression of retinal diabetic microangiopathy.