Apolipoprotein (a) Impairs Endothelial Progenitor Cell-Mediated Angiogenesis

Abstract

Improvement of blood flow and promotion of angiogenesis are important therapeutic measures for the treatment of ischemic peripheral vascular diseases. Since apolipoprotein (a) (apo (a)) is a glycoprotein with repetitive kringle domains exhibiting 75% to 98% structural homology with plasminogen (Plg), apo (a) may also have a negative effect on endothelial progenitor cell (EPC)-induced angiogenesis through Plg-like inhibitory effects on EPC proliferation, adhesion, migration, and angiogenesis. To evaluate the effect of apo (a) on EPCs-induced angiogenesis, EPCs were isolated from the bone marrow of apo (a) transgenic mice, wild-type litter mates, and normal mice. These cells were cultured without or with apo (a) before transplantation. Hindlimb ischemia models were surgically induced in mice, which then received an intravenous injection of 3 · 10 5 EPCs. At 3, 7, and 14 days post EPC transplantation, the adhesion, migration abilities, and capillary density in calf muscles were assessed. Results indicate that apo (a) significantly reduced the adhesion and migration abilities of EPCs. Furthermore, the tubule-like formation of EPCs on Matrigel gels was damaged. In vivo experiments showed the homing of EPCs to ischemic peripheral vascular, and the number of capillary vessels decreased significantly in apo(a) transgenic mice. This study demonstrated that apo (a) could attenuate the adhesion, migration, and homing abilities of EPCs and could impair the angiogenesis ability of EPCs.

Lipoprotein(a): Just an Innocent Bystander in Arterial Hypertension?

“…Moreover, Lp(a) is the preferential lipoprotein carrier of oxidized phospholipids (OxPLs), markedly increasing its proinflammatory properties in comparison to other atherogenic lipoproteins [81,82,157,158]. Once retained and oxidized, Lp(a) modifies the properties of endothelial cells (ECs) that are shifted towards a more inflammatory phenotype characterized by: (a) enhanced expression of cell adhesion molecules (VCAM-1, E-selectin, and ICAM-1) [159,160]; (b) increased oxidative stress with increased generation of reactive oxygen species leading to accelerated senescence [161] and disruption of the integrity of ECs, leading in turn to increased permeability of the endothelial monolayer [162]; (c) enhanced contraction and loss of contact of ECs due to increased phosphorylation of myosin light chains and rearrangement of actin cytoskeleton through the Rho/Rho-kinase-dependent signaling pathway [163,164]; (d) impaired adhesion and migration of endothelial progenitor cells (EPCs) [165]; (e) impairment of angiogenesis signaling pathways and enhanced ECs apoptosis [166] (Figure 2). In animal models, high Lp(a) levels impair endothelium-dependent vasodilation, as demonstrated by a dose-dependent reduction in the expression of inducible nitric oxide synthase, both at mRNA and protein level [167,168].…”

Pro-angiogenic effect of RANTES-loaded polysaccharide-based microparticles for a mouse ischemia therapy

“…It is worth noting that negative control MP had no significant effect. We then sacrificed the animals at day 10 which corresponds to the period required to observe endothelial progenitor cell (EPC) recruitment to injured muscles and their regeneration 26 , 27 .…”

The association between pregnancy levels of blood lipids and the risk of preterm birth

“…It helps transport cholesterol from tissues to the liver for removal, playing a role in preventing cardiovascular diseases like atherosclerosis. However, previous studies have also shown that AopA may also negatively affect endothelial progenitor cell (EPC) -induced angiogenesis by inhibiting EPC proliferation, adhesion, migration, and angiogenesis 26 . Although ApoA is a major component of HDL, our study did not find a link between HDL and PTB.…”