Apolipoprotein A1 (ApoA1) and apolipoprotein E (ApoE) mimetic peptides have attracted attention due to their ability to reduce atherosclerosis and exhibit antioxidant, anti-inflammatory, and hypolipidemic properties.
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.
Animal studies suggest that administration of apolipoprotein A-I, the main protein constituent of HDL, can prevent transplant arteriosclerosis. apoA-I administration increases CEC of HDL.
ATP-binding cassette transporter A1 (ABCA1) promotes cholesterol and phospholipid efflux from cells to lipid-poor apolipoprotein A-I and plays an important role in atherosclerosis.
Genome wide association study (GWAS) studies in humans and hybrid mouse diversity panel (HMDP) studies looking for genetic variants associated with apoA-I or HDL cholesterol levels with cardiovascular disease and atherosclerosis have not provided strong evidence for their atheroprotective function.
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.
In previous work, we reported that helper-dependent adenoviral (HDAd) overexpression of apolipoprotein A-I (apoAI) in endothelial cells (ECs) increases cholesterol efflux in vitro and reduces atherosclerosis in vivo.
In summary, by showing that Lp(a) concentrations and apo(a) apparent size are highly correlated with the ratio of Kringle IV/Kringle V encoding domains in the apo(a) gene, we provide a DNA marker for this atherosclerosis risk factor as well as an important insight into the genetic mechanism regulating Lp(a) levels.
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.
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.
However, apoA1 overexpression has more dramatic protective effects on atherosclerosis in apoE0 mice, which are not significantly reversed by concomitant expression of CETP.
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.
For the current analyses, baseline (2000-2002) plasma total apoC-III and apolipoprotein A-I concentrations of HDL containing or lacking apoC-III were newly measured via sandwich ELISA in 4579 participants from the Multi-Ethnic Study of 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.
Amyloidogenic mutations in human apolipoprotein A-I are not necessarily destabilizing - a common mechanism of apolipoprotein A-I misfolding in familial amyloidosis and atherosclerosis.
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.
ApoA-I potently suppresses LPS-induced atherosclerosis by inhibiting the inflammatory response possibly via activation of STAT3 and upregulation of TTP.
A major mechanism by which apolipoprotein A-I inhibits atherosclerosis may be by promoting cholesterol efflux from macrophages and returning it to the liver for excretion, a process termed reverse cholesterol transport.
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.