We previously reported that EC-directed gene therapy with a helper-dependent adenovirus (HDAd) expressing apolipoprotein A-I (apo A-I) retarded development of atherosclerosis in rabbit carotid arteries over a 1-month interval.
We hypothesized that apoA-I oxidation by MPO levels similar to those present in the artery walls in atherosclerosis can promote apoA-I structural changes and amyloid fibril formation.
We have recently reported that the human apolipoprotein A-I (apoA-I) and apolipoprotein C-III (apoC-III) genes are physically linked and that the presence of a DNA insertion in the apoA-I gene is correlated with apoA-I-apoC-III deficiency in patients with premature atherosclerosis.
We examined how point mutations associated with hereditary amyloidosis (F71Y and L170P) or atherosclerosis (L159R) influence the local apoA-I conformation in model lipoproteins.
We aim to specifically examine apolipoprotein A-I (apoA-I) and apoE mimetic peptides and their role in cholesterol transport during atherosclerosis, suppressors of cytokine signaling (SOCS)1-derived peptides and annexin-A1 as potent inhibitors of inflammation, incretin mimetics and their function in glucose-insulin tolerance, among others.
Unlike in the adult population, serum ApoA-1, ApoB, and ApoB/ApoA-1 ratio may not have significant advantage over conventional lipoproteins in evaluating the presence of systemic inflammation, MS, and risk of atherosclerosis in obese adolescents.
Understanding the features of dysfunctional HDL or apolipoprotein A-I in clinical practice might lead to new diagnostic and therapeutic approaches to atherosclerosis.
Trimeric apoA-I was biologically active in terms of promoting cholesterol efflux, stimulation of lecithin cholesterol acyltransferase-mediated cholesterol esterification, and reducing progression of atherosclerosis in cholesterol-fed low-density lipoprotein receptor-deficient mice.
Treatment with the monoclonal antibody E06 or with apolipoprotein A-I mimetic peptide D-4F, capturing OxPAPC in atherosclerosis, prevented inflammatory hyperalgesia, and in vitro TRPA1 activation.
To determine whether these two HDL populations have different effects on atherogenesis, human apoA-I (AI) and human apoA-I and apoA-II (AI/AII) transgenic mice were produced in an atherosclerosis-susceptible strain.
This is the first study to assess the role of waist-to-hip ratio in explaining race differences in levels of serum apolipoprotein A1, a protective risk factor for atherosclerosis.
These results indicate that the function of lipid-poor apoA-I is not limited to the efflux of cholesterol and phospholipids but suggest that apoA-I serves as a major regulator of the foam cell lipidome and might play an important role in reducing multiple lipid species involved in the pathogenesis of atherosclerosis.
These results demonstrate that Apoa1/c3/a4(-/-) mice display clinical features similar to human apoA-I/C-III/A-IV deficiency (i.e., marked hypoalphalipoproteinemia) and provide further support for the apoa1/c3/a4 gene cluster as a minor susceptibility locus for atherosclerosis in mice.
These results argue for a protective effect of EGCG on apoA-I amyloid associated with atherosclerosis and suggest that EGCG-induced remodeling of amyloid may be tightly regulated by GAGs and other amyloid co-factors <i>in vivo</i>, depending on EGCG bioavailability.
These findings suggest that natural apoA-I mutations L141RPisa and L159RFIN affect the biogenesis and the functionality of HDL in vivo and predispose to diet-induced atherosclerosis in the absence of any other genetic defect.
These data indicate that RVX-208 increases ApoA-I production through an epigenetic mechanism and suggests that BET inhibition may be a promising new approach to the treatment of atherosclerosis.
The presence of a damaging mutation in ABCA1 or APOA1 confers an increased risk of atherosclerosis relative to patients without such a mutation at a comparable level of HDL cholesterol, possibly because of a reduction in CEC.
The potential benefits of high-density lipoproteins (HDL) against atherosclerosis are attributed to its major protein component, apolipoprotein A-I (apoA-I).
The patient had a medical history of atherosclerosis in the coronary and carotid arteries going back 40 years and splenohepatomegalia for 13 years, with a low plasma HDL-C level (0.66 mmol/l) and apolipoprotein A1 level (0.61 mmol/l).
The molecular genetic defect of a female patient with apolipoprotein A-I (apoA-I) deficiency and premature atherosclerosis was examined.Her parents were first cousins.
The loci on 12q and 15q in the present study confirm previously reported loci for apolipoprotein A-I, while the peak on chromosome 6p lends further support to a locus influencing several phenotypes related to atherosclerosis.
The finding of decreased atherosclerosis in the setting of elevated apo[a] and apoA-I suggests that elevations of apoA-I and HDL have a dominant effect in reducing atherosclerosis susceptibility in various settings, including those not associated with alterations of plasma lipids.
The distribution of apolipoprotein (apo) J during the development of atherosclerosis in the human aorta was evaluated by immununohistochemical observation, together with the other apolipoprotein A-I, A-II, B, C-III, and E. Although apoJ was never observed in the normal aorta (ie, without any intimal lesions or intimal thickening), it was distributed not only in the intima but also in the media of aortas with diffuse, intimal thickening or atherosclerotic lesions.
Synthetic high-density lipoprotein (sHDL) nanoparticles composed of apolipoprotein A-I (ApoA-I) mimetic peptide and phospholipids have been shown to reduce atherosclerosis in animal models.