Quantitation and localization of apolipoproteins [a] and B in coronary artery bypass vein grafts resected at re-operation.

Cushing, Gary L.; Gaubatz, John W.; Nava, M. L.; Burdick, Bethany; Bocan, T. M. A.; Guyton, John R.; Weilbaecher, Donald G.; DeBakey, Michael E.; Lawrie, Gerald M.; Morrisett, Joel D.

doi:10.1161/01.atv.9.5.593

Cited by 249 publications

(76 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Plasma-derived Lp(a) is known to penetrate human arteries 31 and the arteries of mice. 32 Therefore, a high serum Lp(a) concentration might affect blood vessel formation, such as collateral formation in ischemic disease. Nevertheless, none of the studies has documented the effects of high serum Lp(a) concentration on collateral formation because of the lack of adequate animal models.…”

Section: Discussionmentioning

confidence: 99%

Impairment of Collateral Formation in Lipoprotein(a) Transgenic Mice

et al. 2002

View full text Add to dashboard Cite

Background-Although lipoprotein(a) (Lp[a]) is a risk factor for atherosclerosis, no study has documented the effects of Lp(a) on angiogenesis. In this study, we examined collateral formation in peripheral arterial disease (PAD) model in Lp(a) transgenic mice. In addition, we examined the feasibility of gene therapy by using an angiogenic growth factor, hepatocyte growth factor (HGF), to treat PAD in the presence of high Lp(a). Methods and Results-In Lp(a) transgenic mice, the degree of natural recovery of blood flow after operation was significantly lower than that in nontransgenic mice. Of importance, there was a significant negative correlation between serum Lp(a) concentration and the degree of natural recovery of blood flow (PϽ0.05). In addition, Lp(a) significantly stimulated the growth of vascular smooth muscle, accompanied by the phosphorylation of ERK. These data demonstrated the association of impairment of collateral formation with serum Lp(a) concentration. Thus, we examined the feasibility of therapeutic angiogenesis by using HGF, with the goal of progression to human gene therapy. In a large proportion of these patients, the anatomic extent and the distribution of arterial occlusive disease make the patients unsuitable for operative or percutaneous revascularization. Thus, the disease frequently follows an inexorable downhill course. 2,3 One of the risk factors related to peripheral arterial disease is a high concentration of serum lipoprotein(a) (Lp[a]) because Lp(a) is also a risk factor for atherosclerosis, restenosis after angioplasty, ischemic heart disease, and cerebral stroke. 4 -9 Lp(a) consists of LDL with an additional protein component, apolipoprotein (a) (apo [a]), a homologue of plasminogen. 10 Lp(a) and apo(a) have been thought to enhance proliferation of human vascular smooth muscle cells (VSMCs). [11][12][13][14] On the other hand, Lp(a) has been postulated to bind to endothelial cells and macrophages and to extracellular components such as fibrin and inhibit cell-associated plasminogen activation. 15,16 Moreover, the inhibition of activation of transforming growth factor (TGF)-␤ by Lp(a) because of its strong homology to plasminogen has been reported. 11 Because TGF-␤ is also known to have proangiogenic properties, Lp(a) might inhibit angiogenesis from this aspect. In contrast, there is less evidence for the stimulation of Lp(a) on angiogenesis, although the proliferation of VSMCs might promote collateral formation in the case that endothelial cells would be stimulated by Lp(a). Nevertheless, no [17][18][19][20] Thus, a strategy for therapeutic angiogenesis with the use of angiogenic growth factors should be considered for the treatment of patients with critical limb ischemia or myocardial infarction. In addition to VEGF, we and others have reported the angiogenic property of hepatocyte growth factor (HGF) in a rabbit ischemia model. [21][22][23][24] Thus, it is preferable to stimulate angiogenesis by HGF, not only in a normal model but also in other high-risk conditions such as ...

show abstract

Section: Discussionmentioning

confidence: 99%

Impairment of Collateral Formation in Lipoprotein(a) Transgenic Mice

et al. 2002

View full text Add to dashboard Cite

show abstract

“…This is confirmed by the fact that incubation of platelets with physiological concentrations of atherogenic apoB-containing lipoproteins such as LDL or VLDL results in enhanced platelet aggregability [30] while antiatherogenic lipoproteins such as HDL exert the opposite effect [31]. Concerning Lp(a) it is generally accepted that elevated plasma concentrations of this lipoprotein are connected with premature atherosclerosis [32] but much uncertainty remains about the influence of Lp(a) on platelet activation, a phenomenon that is believed to be involved not only in long-term processes of plaque formation but also in acute events such as stroke and myocardial infarction [33]. Moreover a two-fold increase in the risk of coronary heart disease (CHD) and ischaemic stroke could be demonstrated especially in subjects with small apolipoprotein(a) phenotypes [34] and prospective findings in the Bruneck study have revealed a significant association specifically between small apolipoprotein(a) phenotypes and advanced atherosclerotic disease involving a component of plaque thrombosis [35].…”

Section: Lp(a) and Platelet Aggregationmentioning

confidence: 95%

Lipoprotein (a) – An Overview

Gries¹

2012

Lipoproteins - Role in Health and Diseases

View full text Add to dashboard Cite

“…In advanced lesions, Lp(a) is found predominantly in the intima, where it is primarily colocalized with foam cells. 18,19 Lp(a) contributes to the formation of foam cells because it can be oxidized, aggregated, or subjected to phospholipase A 2 modification, and in this form it is taken up by scavenger receptors of macrophages.1 In addition, Lp(a) influences the function of cells that play important roles in atherogenesis, such as monocytes-macrophages and endothelial cells. 6 -8 Unlike Lp(a), the role of Lp-PLA 2 in atherogenesis is less well understood.…”

Section: In Atherogenesismentioning

confidence: 99%

“…18,19 Like LDL, Lp(a) is susceptible to oxidation, and oxidized Lp(a) is enriched in lysophosphatidylcholine (lyso-PC), which is formed by hydrolysis of OxPL, a reaction catalyzed by the endogenous Lp-PLA 2 . 13 Lyso-PC plays important roles in plaque formation; thus, it is considered as an important proatherogenic phospholipid.…”

Section: Lp(a)-associated Lp-pla 2 In Atherosclerosis and Cardiovascumentioning

confidence: 99%

Atherosclerosis and Cardiovascular Disease

Descovich¹,

Gaddi²,

Magri³

et al. 1990

View full text Add to dashboard Cite

Abstract-Lipoprotein(a) [Lp(a)] plays an important role in atherosclerosis. The biological effects of Lp(a) have been attributed either to apolipoprotein(a) or to its low-density lipoprotein-like particle. Lp(a) contains platelet-activating factor acetylhydrolase, an enzyme that exhibits a Ca 2ϩ -independent phospholipase A 2 activity and is complexed to lipoproteins in plasma; thus, it is also referred to as lipoprotein-associated phospholipase A 2 . Substrates for lipoprotein-associated phospholipase A 2 include phospholipids containing oxidatively fragmented residues at the sn-2 position (oxidized phospholipids; OxPLs). OxPLs may play important roles in vascular inflammation and atherosclerosis. Plasma levels of OxPLs present on apolipoprotein B-100 particles (OxPL/apolipoprotein B) are correlated with coronary artery, carotid, and peripheral arterial disease. Furthermore, OxPL/apolipoprotein B levels in plasma are strongly correlated with Lp(a) levels, are preferentially sequestered on Lp(a), and thus are potentially subjected to degradation by the Lp(a)-associated lipoprotein-associated phospholipase A 2 . The present review article focuses specifically on the characteristics of the lipoprotein-associated phospholipase A 2 associated with Lp(a) and discusses the possible role of this enzyme in view of emerging data showing that OxPLs in plasma are preferentially sequestered on Lp(a) and may significantly contribute to the increased atherogenicity of this lipoprotein. (Arterioscler Thromb Vasc

show abstract

Quantitation and localization of apolipoproteins [a] and B in coronary artery bypass vein grafts resected at re-operation.

Cited by 249 publications

References 46 publications

Impairment of Collateral Formation in Lipoprotein(a) Transgenic Mice

Impairment of Collateral Formation in Lipoprotein(a) Transgenic Mice

Lipoprotein (a) – An Overview

Atherosclerosis and Cardiovascular Disease

Contact Info

Product

Resources

About