ArticleThe Journal of biological chemistry2008
Apolipoprotein(a), through its strong lysine-binding site in KIV(10'), mediates increased endothelial cell contraction and permeability via a Rho/Rho kinase/MYPT1-dependent pathway.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 72 citations in OpenAlex.
- The Roles of Lipoprotein(a) in Atherosclerosis - Minding the Knowledge Gaps.Current atherosclerosis reports · 2026Review
- Presumed Mechanisms Underlying Lipoprotein(a)-caused Atherosclerosis.European cardiology · 2026Review
- The biology of lipoprotein(a): From genetics to molecular mechanisms.European journal of clinical investigation · 2026Review
- Influence of LDL cholesterol and Lp(a) on monocytes and macrophages in atherosclerosis.Biochemia medica · 2025Review
- Lipoprotein(a) and panvascular disease.Lipids in health and disease · 2025Review
- Association Between Lipoprotein(a) and Dilatation of Different Aortic Segments in Hypertensive Patients.Echocardiography (Mount Kisco, N.Y.) · 2025Article
- Lipoprotein(a) and cardiovascular disease.The Biochemical journal · 2024Review
- The Role of Lipoprotein(a) in Peripheral Artery Disease.Biomedicines · 2024Review
- Lipoprotein(a): Just an Innocent Bystander in Arterial Hypertension?International journal of molecular sciences · 2023Review
- Lipoprotein(a): a Case for Universal Screening in Youth.Current atherosclerosis reports · 2023Review
- Altered Functionality of Lipoprotein(a) Impacts on Angiogenesis in Diabetic Retinopathy.Investigative ophthalmology & visual science · 2023Article
- Lipoprotein(a) in Atherosclerotic Diseases: From Pathophysiology to Diagnosis and Treatment.Molecules (Basel, Switzerland) · 2023Review
- Lipoprotein(a) induces caspase-1 activation and IL-1 signaling in human macrophages.Frontiers in cardiovascular medicine · 2023Article
- Lipoprotein(a), a Lethal Player in Calcific Aortic Valve Disease.Frontiers in cell and developmental biology · 2022Review
- Mendelian randomization of genetically independent aging phenotypes identifies LPA and VCAM1 as biological targets for human aging.Nature aging · 2022Article
- Lipoprotein (a) and Hypertension.Current hypertension reports · 2021Review
- Lipoprotein (a): When to Measure and How to Treat?Current atherosclerosis reports · 2021Review
- Recent Updates of Lipoprotein(a) and Cardiovascular Disease.Chonnam medical journal · 2021Review
- Identification and analyses of inhibitors targeting apolipoprotein(a) kringle domains KIV-7, KIV-10, and KV provide insight into kringle domain function.The Journal of biological chemistry · 2020Article
- Lipoprotein(a) the Insurgent: A New Insight into the Structure, Function, Metabolism, Pathogenicity, and Medications Affecting Lipoprotein(a) Molecule.Journal of lipids · 2020Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Substantial evidence indicates that endothelial dysfunction plays a critical role in atherogenesis. We previously demonstrated that apolipoprotein(a) (apo(a); the distinguishing protein component of the atherothrombotic risk factor lipoprotein(a)) elicits rearrangement of the actin cytoskeleton in human umbilical vein endothelial cells, characterized by increased myosin light chain (MLC) phosphorylation via a Rho/Rho kinase-dependent signaling pathway. Apo(a) contains kringle (K)IV and KV domains similar to those in plasminogen: apo(a) contains 10 types of plasminogen KIV-like sequences, followed by sequences homologous to the plasminogen KV and protease domains. Several of the apo(a) kringles contain lysine-binding sites (LBS) that have been proposed to contribute to the pathogenicity of Lp(a). Here we demonstrate that apo(a)-induced endothelial barrier dysfunction is mediated via a Rho/Rho kinase-dependent signaling pathway that results in increased MYPT1 phosphorylation and hence decreased MLC phosphatase activity, thus leading to an increase in MLC phosphorylation, stress fiber formation, cell contraction, and permeability. In addition, studies using recombinant apo(a) variants indicated that these effects of apo(a) are dependent on sequences within the C-terminal half of the apo(a) molecule, specifically, the strong LBS in KIV(10). In parallel experiments, the apo(a)-induced effects were completely abolished by treatment of the cells with the lysine analogue epsilon-aminocaproic acid and the Rho kinase inhibitor Y27632. Taken together, our findings indicate that the strong LBS in apo(a) KIV(10) mediates all of our observed effects of apo(a) on human umbilical vein endothelial cell barrier dysfunction. Studies are ongoing to further dissect the molecular basis of these findings.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.