Exploiting the Vascular Protective Effects of High-Density Lipoprotein and its Apolipoproteins

Shah, Prediman K.; Kaul, Sanjay; Nilsson, Jan; Cercek, Bojan

doi:10.1161/hc4501.098468

Cited by 176 publications

(98 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, apoA-1 mimetics may be able to protect endothelial function against vascular disease driven by chronic states of inflammation. Finally, as apoA-1 mimetics are designed to increase HDL function, 6,7,10,26 our findings support the concept that HDL plays a critical role in maintaining vascular function 4,5 in diseases that are as distinct as hypercholesterolemia and sickle cell. Institute (HL 61417 and HL71214 to Dr Pritchard; HL44612 and HL70981 to Dr Hillery; and HL65203, HL68769, and VA Merit Review to Dr Gutterman).…”

Section: Discussionsupporting

confidence: 68%

“…2,3 Recently, it was suggested that high-density lipoprotein (HDL) might be an important therapeutic target for atheroprotection. 4,5 Apolipoprotein (apo) A-1 mimetics have been shown to increase HDL function to inhibit atherosclerosis 6 and restore antiinflammatory and antioxidant properties to HDL that are lost during influenza infection. 7 HDL serves many functions, eg, reverse cholesterol transport, removal of seeding molecules of oxidized lipids from LDL that inhibit subsequent oxidation, and inhibition of LDL-induced monocyte chemotactic protein-1 activity.…”

mentioning

confidence: 99%

See 1 more Smart Citation

L-4F, an Apolipoprotein A-1 Mimetic, Dramatically Improves Vasodilation in Hypercholesterolemia and Sickle Cell Disease

et al. 2003

View full text Add to dashboard Cite

Background-Hypercholesterolemia and sickle cell disease (SCD) impair endothelium-dependent vasodilation by dissimilar mechanisms. Hypercholesterolemia impairs vasodilation by a low-density lipoprotein (LDL)-dependent mechanism. SCD has been characterized as a chronic state of inflammation in which xanthine oxidase (XO) from ischemic tissues increases vascular superoxide anion (O 2 ·Ϫ ) generation. Recent reports indicate that apolipoprotein (apo) A-1 mimetics inhibit atherosclerosis in LDL receptor-null (Ldlr Ϫ/Ϫ ) mice fed Western diets. Here we hypothesize that L-4F, an apoA-1 mimetic, preserves vasodilation in hypercholesterolemia and SCD by decreasing mechanisms that increase O 2 ·Ϫ generation. Methods and Results-Arterioles were isolated from hypercholesterolemic LdlrϪ/Ϫ mice and from SCD mice that were treated with either saline or L-4F (1 mg/kg per day). Vasodilation in response to acetylcholine was determined by videomicroscopy. Effects of L-4F on LDL-induced increases in endothelium-dependent O 2 ·Ϫ generation were determined on arterial segments via the hydroethidine assay and on stimulated endothelial cell cultures via superoxide dismutase-inhibitable ferricytochrome c reduction. Effects of L-4F on XO bound to pulmonary arterioles and content in livers of SCD mice were determined by immunofluorescence. Hypercholesterolemia impaired vasodilation in Ldlr Ϫ/Ϫ mice, which L-4F dramatically improved. L-4F inhibited LDL-induced increases in O 2 ·Ϫ in arterial segments and in stimulated cultures. SCD impaired vasodilation, increased XO bound to pulmonary endothelium, and decreased liver XO content. L-4F dramatically improved vasodilation, decreased XO bound to pulmonary endothelium, and increased liver XO content compared with levels in untreated SCD mice. Conclusions-These data show that L-4F protects endothelium-dependent vasodilation in hypercholesterolemia and SCD.Our findings suggest that L-4F restores vascular endothelial function in diverse models of disease and may be applicable to treating a variety of vascular diseases. Clinical studies clearly indicate that HDL plays an important role in protecting vascular function against atherosclerosis. 8 Transgenic expression of apoA-1, the major atheroprotective apolipoprotein of HDL, retards the progression of advanced lesions in transplanted aortas from apoE-null mice and remodels them to a more stable-appearing phenotype. 9 Intraperitoneal injection of an apoA-1 mimetic (5F) and parental administration of another apoA-1 mimetic (D-4F) enhances the ability of HDL to inhibit LDL oxidation and to protect mice from diet-induced atherosclerosis without changing plasma cholesterol levels. 6,10 Indeed, infusion of reconstituted HDL rapidly improves endothelium-and endothelial nitric oxide synthase (eNOS)-dependent forearm blood flow in hypercholesterolemic men, 11 confirming that HDL plays a critical role in protecting endothelial cell function.The mechanisms by which SCD have been shown to impair vasodilation at first glance appear distinctly different from tho...

show abstract

Section: Discussionsupporting

confidence: 68%

mentioning

confidence: 99%

L-4F, an Apolipoprotein A-1 Mimetic, Dramatically Improves Vasodilation in Hypercholesterolemia and Sickle Cell Disease

et al. 2003

View full text Add to dashboard Cite

show abstract

“…O perfil lipídico, embora desejável, mostra valores reduzidos de HDLc nos pacientes, sugerindo menor proteção contra aterosclerose nesses indivíduos [18][19][20] . Apesar disso, valores mais elevados de HDLc são observados nesse grupo no sexo feminino, refletindo padrões estritamente fisiológicos ou influência do uso de anticoncepcionais ou terapia de reposição hormonal 21 .…”

Section: Discussionunclassified

Prevalência de síndrome metabólica em indivíduos brasileiros pelos critérios de NCEP-ATPIII e IDF

Nakazone¹,

Pinheiro²,

Braile³

et al. 2007

Rev. Assoc. Med. Bras.

View full text Add to dashboard Cite

“…1,2 Direct vascular protective effects of HDL have been attributed to apolipoprotein (apo) A-I or apoA-I-associated molecules in HDL using direct intravenous injections of homologous HDL, 3 recombinant mutant apoA-I milano 4 -8 or apoA-I gene therapy, 9 -11 or use of transgenic animals overexpressing apoA-I [11][12][13][14][15][16][17] or apoA-I-related molecules such as paraoxonase. 18 A recent phase II randomized trial showed that 5 weekly intravenous injections of recombinant apoA-1 milano induced rapid regression of coronary atherosclerotic lesions in humans.…”

mentioning

confidence: 99%

Differential Effects of Apolipoprotein A-I–Mimetic Peptide on Evolving and Established Atherosclerosis in Apolipoprotein E-Null Mice

et al. 2004

Self Cite

View full text Add to dashboard Cite

Background-Apolipoprotein (apo) A-I and apoA-I-mimetic peptides showed promise to prevent atherosclerosis development. Using a bypassed vein graft model in apoE-null mice, we evaluated the effects of oral or intraperitoneal administration of an apoA-I-mimetic peptide on evolving atherosclerotic lesions in the vein graft and compared such effects on the established atherosclerotic lesions in aortic sinus in the same mice. Methods and Results-We used apoE-null mice in which a segment of inferior vena cava was grafted into the right carotid artery at 16 weeks of age. Native aortic atherosclerotic lesions (established atherosclerosis) and vein-graft atherosclerotic lesions (evolving atherosclerosis) were assessed 4 weeks after daily oral (0.3 mg/mL) or intraperitoneal (50 g in 200 L saline) administration of an apoA-I-mimetic peptide, D4F. Mice receiving saline or water without D4F served as controls. Both oral and intraperitoneal administration of D4F reduced vein-graft atherosclerotic (evolving lesions) plaque size by 43% and 42%, plaque lipid by 70% and 49%, and macrophage immunoreactivity by 63% and 62%, respectively, compared with controls. In contrast, D4F had no effect on the native aortic sinus atherosclerotic lesions (established lesions). Conclusions-Oral and intraperitoneal administration of the apoA-I-mimetic peptide D4F significantly reduced rapidly evolving atherosclerotic lesions in vein grafts but not established atherosclerotic lesions in aortic sinus. These observations suggest that the type of atherosclerotic lesions and the time of initiation during the course of lesion evolution modulate the beneficial effects of apoA-I-mimetic peptides on atherosclerosis.

show abstract

Exploiting the Vascular Protective Effects of High-Density Lipoprotein and its Apolipoproteins

Cited by 176 publications

References 92 publications

L-4F, an Apolipoprotein A-1 Mimetic, Dramatically Improves Vasodilation in Hypercholesterolemia and Sickle Cell Disease

L-4F, an Apolipoprotein A-1 Mimetic, Dramatically Improves Vasodilation in Hypercholesterolemia and Sickle Cell Disease

Prevalência de síndrome metabólica em indivíduos brasileiros pelos critérios de NCEP-ATPIII e IDF

Differential Effects of Apolipoprotein A-I–Mimetic Peptide on Evolving and Established Atherosclerosis in Apolipoprotein E-Null Mice

Contact Info

Product

Resources

About