Apo E4 and lipoprotein-associated phospholipase A2 synergistically increase cardiovascular risk

Abstract

Objective Apolipoprotein E (apoE) has been implicated as conveying increased risk for coronary artery disease (CAD). Previous studies suggest a role of apoE as a modulator of immune response and inflammatory properties. We hypothesized that the presence of apo E4 is associated with an increased inflammatory burden in subjects with CAD as compared to subjects without CAD. Methods ApoE genotypes, systemic (C-reactive protein [CRP], fibrinogen, serum amyloid-A [SAA]) and vascular inflammatory markers (Lipoprotein-associated phospholipase A2 [Lp-PLA2] and pentraxin-3 [PTX-3]) were assessed in 324 Caucasians and 208 African Americans, undergoing coronary angiography. Results For both ethnic groups, Lp-PLA2 index, an integrated measure of Lp-PLA2 mass and activity, increased significantly and stepwise across apoE isoforms (P=0.009 and P=0.026 for African Americans and Caucasians respectively). No differences were found for other inflammatory markers tested (CRP, fibrinogen, SAA and PTX-3). For the top cardiovascular score tertile, apo E4 carriers had a significantly higher level of Lp-PLA2 index in both ethnic groups (P=0.027 and P=0.010, respectively). Conclusion The presence of the apo E4 isoform was associated with a higher level of Lp-PLA2 index, a marker of vascular inflammation. Our results suggest that genetic variation at the apoE locus may impact cardiovascular disease risk through enhanced vascular inflammation.

Apolipoprotein E genotype, TNF-α 308G/A and risk for cardiac surgery associated-acute kidney injury in Caucasians

“…The gene locus for the three major ApoE alleles (E2,E3,E4) is located on chromosome 19q13.2 and the E4 allele has been validated as a strong predictor for Alzheimer's disease. 15 Furthermore, ApoE variants increase cardiovascular disease risks by altering vascular inflammation, 16 and patients carrying the E4 allele are more likely to require CABG at a younger age. 17 In chronic renal failure, Arikan et al showed an association between ApoE genotypes an atherogenic lipid levels in dialysis patients.…”

Review of ‘the Potential Role of Arterial Stiffness in the Pathogenesis of Alzheimer’s Disease’

“…Although traditionally considered clinically distinct from each other with mutually exclusive mechanisms [3] , late-onset AD is increasingly regarded as a pathological process that is strongly influenced by cerebrovascular dysfunction. Even the major single gene associated with increased late-onset AD risk, APOE , was earlier identified as a risk gene for cardiovascular diseases [4] . The pathogenic mechanisms underlying these two conditions appear to be connected through cerebral hypoperfusion, blood–brain barrier compromise, inflammatory cell infiltration and hemorrhagic susceptibility [5–9] .…”

Isolation of Proteins which Interact with Phospholipase A2 (IIA) from Human Serum after Myocardial Infarction. Flavonoids from Bidens tripartita Extract as Phospholipase A2 Inhibitors

“…In this case, the biggest fraction was also albumins (65−70 kDa) (He et al, 1992), but we can observe differences between sample 2 and sample 3: in both of them, protein of 25−30 kDa is presented. According to Gungor et al (2012), apolipoprotein E (APOE) can play an important role in increasing the risk of coronary heart disease; APOE is a 299 amino acids long, arginine-rich protein at 34.2 kDa weight (Ćwiklińska et al, 2015). Previous studies were related only to the study of the concentration of apoE and Lp-PLA 2 in blood plasma of patients using standard clinical procedures.…”