Looking at Lp(a) and Related Cardiovascular Risk: from Scientific Evidence and Clinical Practice

Stulnig, Thomas; Morozzi, Claudia; Reindl‐Schwaighofer, Roman; Stefanutti, Claudia

doi:10.1007/s11883-019-0803-9

Cited by 19 publications

(17 citation statements)

References 43 publications

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“…Lipoprotein(a) is believed to promote atherothrombosis due to its homology with plasminogen [ 5 ]. As indicated, one of the component proteins of Lp(a), apo(a), shares more than 80% of its protein sequence with plasminogen [ 64 ]. Lp(a) lacks KI to KIII of plasminogen, but it contains KIV and KV [ 60 ].…”

Section: Lipoprotein(a) and Atherothrombosismentioning

confidence: 99%

“…Elevated Lp(a) levels are correlated with reduced fibrin clot permeability and impaired fibrinolysis [ 61 ]. Lp(a) competes with plasminogen and tPA for binding sites on fibrin, and consequently, it impairs fibrinolysis [ 1 , 60 , 64 ]. These antifibrinolytic effects are more profound for smaller-sized isoforms of Lp(a), because these have a higher affinity for their binding to fibrin [ 80 ].…”

Section: Lipoprotein(a) and Atherothrombosismentioning

confidence: 99%

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Lipoprotein(a)—The Crossroads of Atherosclerosis, Atherothrombosis and Inflammation

Ugovšek

Šebeštjen

2021

Biomolecules

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Increased lipoprotein(a) (Lp(a)) levels are an independent predictor of coronary artery disease (CAD), degenerative aortic stenosis (DAS), and heart failure independent of CAD and DAS. Lp(a) levels are genetically determinated in an autosomal dominant mode, with great intra- and inter-ethnic diversity. Most variations in Lp(a) levels arise from genetic variations of the gene that encodes the apolipoprotein(a) component of Lp(a), the LPA gene. LPA is located on the long arm of chromosome 6, within region 6q2.6–2.7. Lp(a) levels increase cardiovascular risk through several unrelated mechanisms. Lp(a) quantitatively carries all of the atherogenic risk of low-density lipoprotein cholesterol, although it is even more prone to oxidation and penetration through endothelia to promote the production of foam cells. The thrombogenic properties of Lp(a) result from the homology between apolipoprotein(a) and plasminogen, which compete for the same binding sites on endothelial cells to inhibit fibrinolysis and promote intravascular thrombosis. LPA has up to 70% homology with the human plasminogen gene. Oxidized phospholipids promote differentiation of pro-inflammatory macrophages that secrete pro-inflammatory cytokines (e. g., interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α). The aim of this review is to define which of these mechanisms of Lp(a) is predominant in different groups of patients.

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Section: Lipoprotein(a) and Atherothrombosismentioning

confidence: 99%

Section: Lipoprotein(a) and Atherothrombosismentioning

confidence: 99%

Lipoprotein(a)—The Crossroads of Atherosclerosis, Atherothrombosis and Inflammation

Ugovšek

Šebeštjen

2021

Biomolecules

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“…It is synthesized in the liver and catabolized in the liver and kidneys. In patients with chronic kidney disease, the level of Lp(a) is elevated due to decreased excretion [156][157][158][159] Physiologically, Lp(a) participates in thrombogenesis, wound healing, tissue repair, and vascular remodeling [154,160]. Part of its thrombogenicity comes from apo(a), which is a structural homolog to plasminogen.…”

Section: Lipoprotein(a)mentioning

confidence: 99%

Lipids and Lipoproteins in Health and Disease: Focus on Targeting Atherosclerosis

et al. 2021

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Despite advances in pharmacotherapy, intervention devices and techniques, residual cardiovascular risks still cause a large burden on public health. Whilst most guidelines encourage achieving target levels of specific lipids and lipoproteins to reduce these risks, increasing evidence has shown that molecular modification of these lipoproteins also has a critical impact on their atherogenicity. Modification of low-density lipoprotein (LDL) by oxidation, glycation, peroxidation, apolipoprotein C-III adhesion, and the small dense subtype largely augment its atherogenicity. Post-translational modification by oxidation, carbamylation, glycation, and imbalance of molecular components can reduce the capacity of high-density lipoprotein (HDL) for reverse cholesterol transport. Elevated levels of triglycerides (TGs), apolipoprotein C-III and lipoprotein(a), and a decreased level of apolipoprotein A-I are closely associated with atherosclerotic cardiovascular disease. Pharmacotherapies aimed at reducing TGs, lipoprotein(a), and apolipoprotein C-III, and enhancing apolipoprotein A-1 are undergoing trials, and promising preliminary results have been reported. In this review, we aim to update the evidence on modifications of major lipid and lipoprotein components, including LDL, HDL, TG, apolipoprotein, and lipoprotein(a). We also discuss examples of translating findings from basic research to potential therapeutic targets for drug development.

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“…In 2009, an Italian multicentric study demonstrated that long term apheresis stopped the evolution of cardiovascular disease in high risk patients with Lp(a) hyperlipoproteinemia. A longitudinal cohort multicentric study on 120 subjects with coronary heart disease and Lp(a) hyperlipoproteinemia, treated with apheresis and maximum lipid lowering therapy, showed Lp(a) reduction by 73.3% with a subsequent decrease in annual cardiovascular CV events by 86.4% [64]. In 2010, Stefanutti et al [65], in a study which enrolled 21 patients with documented coronary artery disease (CAD), demonstrated Lp(a) reduction by 57.8 ± 9.5% in patients on apheresis and Lp(a) increase by 14.7 ± 36.5% in a control group.…”

Section: Apheresismentioning

confidence: 99%

Lipoprotein(a) Where Do We Stand? From the Physiopathology to Innovative Terapy

et al. 2021

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A number of epidemiologic studies have demonstrated a strong association between increasing lipoprotein a [Lp(a)] and cardiovascular disease. This correlation was demonstrated independent of other known cardiovascular (CV) risk factors. Screening for Lp(a) in the general population is not recommended, although Lp(a) levels are predominantly genetically determined so a single assessment is needed to identify patients at risk. In 2019 ESC/EAS guidelines recommend Lp(a) measurement at least once a lifetime, fo subjects at very high and high CV risk and those with a family history of premature cardiovascular disease, to reclassify patients with borderline risk. As concerning medications, statins play a key role in lipid lowering therapy, but present poor efficacy on Lp(a) levels. Actually, treatment options for elevated serum levels of Lp(a) are very limited. Apheresis is the most effective and well tolerated treatment in patients with high levels of Lp(a). However, promising new therapies, in particular antisense oligonucleotides have showed to be able to significantly reduce Lp(a) in phase II RCT. This review provides an overview of the biology and epidemiology of Lp(a), with a view to future therapies.

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Looking at Lp(a) and Related Cardiovascular Risk: from Scientific Evidence and Clinical Practice

Cited by 19 publications

References 43 publications

Lipoprotein(a)—The Crossroads of Atherosclerosis, Atherothrombosis and Inflammation

Lipoprotein(a)—The Crossroads of Atherosclerosis, Atherothrombosis and Inflammation

Lipids and Lipoproteins in Health and Disease: Focus on Targeting Atherosclerosis

Lipoprotein(a) Where Do We Stand? From the Physiopathology to Innovative Terapy

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