Angiogenesis is a finely co-ordinated, multi-step developmental process of the new
vascular structure. Even though angiogenesis is regularly occurring in physiological
events such as embryogenesis, in adults, it is restricted to specific tissue sites
where rapid cell-turnover and membrane synthesis occurs. Both excessive and insufficient
angiogenesis lead to vascular disorders such as cancer, ocular diseases, diabetic
retinopathy, atherosclerosis, intra-uterine growth restriction, ischemic heart disease,
stroke etc. Occurrence of altered lipid profile and vascular lipid deposition along
with vascular disorders is a hallmark of impaired angiogenesis. Among lipoproteins,
lipoprotein(a) needs special attention due to the presence of a multi-kringle protein
subunit, apolipoprotein(a) [apo(a)], which is structurally homologous to many naturally
occurring anti-angiogenic proteins such as plasminogen and angiostatin. Researchers
have constructed different recombinant forms of apo(a) (rhLK68, rhLK8, RHACK2, KV-11,
and AU-6) and successfully exploited its potential to inhibit unwanted angiogenesis
during tumor metastasis and retinal neovascularization. Similar to naturally occurring
anti-angiogenic proteins, apo(a) can directly interfere with angiogenic signaling
pathways. Besides this, apo(a) can also exert its anti-angiogenic effect indirectly
by inducing endothelial cell apoptosis, by inhibiting endothelial progenitor cell
functions or by upregulating nuclear factors in endothelial cells via apo(a)-bound
oxPLs. However, the impact of the anti-angiogenic potential of native apo(a) during
physiological angiogenesis in embryos and wounded tissues is not yet explored. In
this context, we review the studies so far done to demonstrate the anti-angiogenic
activity of apo(a) and the recent developments in using apo(a) as a therapeutic agent
to treat impaired angiogenesis during vascular disorders, with emphasis on the gaps
in the literature.