LPA Specific Neutra™ Antibody Products

Lipoprotein(a), abbreviated as LPA, functions as a serine protease that suppresses the activity of tissue-type plasminogen activator I. This encoded protein forms a significant component of lipoprotein and undergoes proteolytic cleavage, producing fragments that adhere to atherosclerotic plaques and facilitate thrombogenesis. Increased levels of LPA in the bloodstream correlate with heightened susceptibility to developing atherosclerosis. Conditions linked to LPA include lipoprotein quantitative trait locus and atherosclerosis. Relevant pathways involving LPA include plasma lipoprotein assembly, remodeling, and clearance, as well as cholesterol metabolism.

Its Gene ID: 4018, UniProtKB ID: P08519, and OMIM ID: 152200.

LPA Related Pathway

LPA consists of a low-density lipoprotein (LDL)-like particle, where apolipoprotein B-100 (apoB) is covalently bonded to the hydrophilic, glycosylated apo(a). Additionally, there exists an LPA catabolism pathway involving the recycling of apo(a). Multiple hepatic receptors participate in LPA catabolism. PlgRKT mediates a futile cycle involving the uptake of LPA and apo(a) in Rab5 early endosomes, followed by apo(a) recycling through Rab11 recycling endosomes. The secreted apo(a) can rebind to newly-formed or circulating LDL, forming new LPA. LDLR and LRP1 serve as PCSK9-sensitive clearance receptors, where LPA competes with TRLs, a competition modulated by the apoE genotype. This clathrin-mediated endocytosis pathway leads to lysosomal degradation of LPA's lipid moiety and the associated apo(a). Additionally, receptors like SR-BI are implicated in the lysosomal degradation of the entire particle or its lipid content.

Fig.1 Diagram illustrating the routes of cholesterol and lipoprotein metabolism along with the associated genes.^{1, 3}

Applications of Anti-LPA Antibodies

• Role of Anti-LPA Antibodies in Atherogenesis Treatment

Plasma concentrations of LPA exceeding a level are correlated with heightened risks of myocardial infarction and stroke. LPA contains apo(a), a plasminogen-like glycoprotein. To evaluate apo(a)'s capability to covalently bind human apoB-100 and form LPA, plasma from an apo(a)-expressing mouse is incubated with plasma from a human apoB-100 transgenic mouse, followed by SDS-PAGE separation and immunoblotting with anti-LPA antibodies. The results indicate the formation of a larger LPA complex due to the disulfide linkage between apo(a) and human apoB-100. An enzyme-linked sandwich assay with anti-LPA monoclonal antibody reveals elevated levels of oxidized phospholipids in LPA from high-expressing mice, unlike in LDL from low-expressing mice or human apoB-100 transgenic mice, despite similar plasma levels of human apoB-100 across all mice. This increase in oxidized lipids specific to LPA in high-level apo(a)-expressing mice suggests a mechanism by which elevated circulating LPA levels may contribute to atherogenesis.

Fig.2 Immunoblotting result of LPA formation.^{2, 3}

Creative Biolabs offers a diverse array of over 10 meticulously engineered antibodies targeting LPA, developed through advanced recombinant technologies. Additionally, bespoke customization services are available to design neutralizing antibodies specific to LPA, tailored to exact specifications.

REFERENCES

1. Paththinige, C. S., N. D. Sirisena, and V. H. W. Dissanayake. "Genetic determinants of inherited susceptibility to hypercholesterolemia–a comprehensive literature review." Lipids in health and disease 16 (2017): 1-22.
2. Schneider, Matthias, et al. "High-level lipoprotein [a] expression in transgenic mice: evidence for oxidized phospholipids in lipoprotein [a] but not in low density lipoproteins." Journal of lipid research 46.4 (2005): 769-778.
3. Distributed Under open access license CC BY 4.0, without modification.