Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease?

Boffa, Michael B.; Koschinsky, Marlys L.

doi:10.1194/jlr.r060582

Cited by 192 publications

(125 citation statements)

References 144 publications

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“…Increased Lipoprotein (a) and homocysteine were the most frequently observed prothrombotic factors in LV patients. Both factors are aligned with an increased risk for venous and arterial thrombosis [29][30][31] and had been associated with LV before. 27,32,33 Additional prothrombotic factors were found in this study that related to LV.…”

Section: Discussionmentioning

confidence: 99%

Characteristics, risk factors and treatment reality in livedoid vasculopathy – a multicentre analysis

Weishaupt

Strölin

Kahle³

et al. 2019

Acad Dermatol Venereol

105

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Background Livedoid vasculopathy (LV) is a rare cutaneous thrombotic disease. It is characterized by occlusion of dermal vessels resulting in livedo racemosa, ulceration and atrophie blanche. Clear guidelines for diagnosis and treatment are missing. Objective The purpose of this study was to better characterize epidemiology, clinical appearance and treatment reality of LV in a well‐defined patient cohort. Methods The cohort was allocated within a prospective, multicentre, phase IIa trial that investigated the effect of rivaroxaban in LV. Results Analysis of 27 patients revealed that LV patients had an increased Body Mass Index (BMI; 11/27), hypertension (19/27) and increased levels of lipoprotein (a) (5/12) and homocysteine (10/12) in the blood. The female‐to‐male ratio was 2.1 : 1, and the median age was 53.0 years [interquartile range (IQR) 40.5–68]. Investigation of the clinical appearance found that 82% of patients had livedo racemosa, and the ankle region was most likely to be affected by ulceration (56–70%). The analysis of patient treatment history showed that heparin was most effective (12/17), while anti‐inflammatory regimens were, although often used (17/24), not effective (0/17). Conclusion We add clinical clues for a data supported diagnosis of LV, and we provide evidence that anticoagulants should be administered in monotherapy first line (EudraCT number 2012‐000108‐13‐DE).

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Section: Discussionmentioning

confidence: 99%

Characteristics, risk factors and treatment reality in livedoid vasculopathy – a multicentre analysis

Weishaupt

Strölin

Kahle³

et al. 2019

Acad Dermatol Venereol

105

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“…However, genetic studies in several tens of thousands of individuals found that neither Lp(a) concentrations nor genetic variants associated with high Lp(a) concentrations were connected with the risk of venous thrombosis or venous thromboembolism (58,59). The role of Lp(a) in coagulation is reviewed elsewhere in this Thematic Review series (57).…”

Section: Structure and Assembly Of The Lp(a) Particlementioning

confidence: 99%

“…fibrinolysis cascades under in vitro conditions (56,57). While apo(a) itself lacks fibrinolytic activity, it is reported to prevent the conversion of PLG to plasmin by inhibiting activators, such as streptokinase, urokinase, and tissue type PLG activator (t-PA) [reviewed in (19)].…”

Section: Structure and Assembly Of The Lp(a) Particlementioning

confidence: 99%

Structure, function, and genetics of lipoprotein (a)

Schmidt

Noureen

Kronenberg

et al. 2016

Journal of Lipid Research

384

328

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between apoB-100 of the LDL moiety and one of the kringle domains in apo(a) (4,5,(14)(15)(16). The assembly of Lp(a) is believed to occur at the hepatocyte cell membrane surface (17), but other scenarios have also been proposed [reviewed in (18, 19)].Lp(a) was originally described as a dichotomous (Lp+, Lp) genetic trait (20), but it soon became evident that it is quantitative rather than qualitative in nature (21-23). Lp(a) plasma concentrations are highly heritable (24-28). The major locus controlling the Lp(a) concentrations is the LPA gene (MIM 152200; ENSG00000198670) on the reverse strand of chromosome 6q27 (29-31), which encodes the apo(a) component of Lp(a) (25,26,(32)(33)(34). Close LPA orthologs are found in all apes and in Old World monkeys. INTRA-AND INTER-POPULATION DIFFERENCES INLp ( INTRODUCTION TO THE LIPOPROTEIN (a) TRAITHuman lipoprotein (a) [Lp(a)] is a macromolecular complex in plasma that was first described in 1963 by the Norwegian physician Kåre Berg (1). Ever since its discovery, this enigmatic particle has intrigued basic researchers and clinicians due to its unknown physiological function and its association with atherosclerotic diseases, in particular coronary heart disease (CHD) [reviewed in (2)]. Lp(a) is composed of one molecule of a LDL-particle containing apoB-100 and one molecule of a large highly polymorphic glycoprotein named apo(a) (3-6). A characteristic feature of apo(a) is the presence of loop-like structures called kringles (7,8). Kringle domains are triple loop structures stabilized by three internal disulfide bonds and are also present in other coagulation factors, such as plasminogen (PLG), prothrombin, urokinase, and tissue-type PLG activators (9-12). In contrast to PLG, the linker domain between kringles is glycosylated in apo(a). The apo(a) is synthesized by the liver (13). The two components of Lp(a) are covalently linked together by a disulfide bond

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“…Accelerating plasminogen activation and protecting plasmin from inhibition represent two mechanisms for how plasminogen receptors promote thrombolysis (Miles et al, ). Lipoprotein(a) may promote a more thrombotic state by a number of mechanisms, including inhibition of the fibrinolytic system and enhancement of the tissue factor‐mediated pathway (Boffa & Koschinsky, ). These effects are illustrated in Figure .…”

Section: Pathophysiological Mechanisms Underlying the Athero‐thrombotmentioning

confidence: 99%

Lipoprotein(a): A missing culprit in the management of athero‐thrombosis?

Ferretti

Bacchetti

Johnston

et al. 2017

Journal Cellular Physiology

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Lipoprotein(a) Lp(a) is a cholesterol-rich, LDL-like particle that is independently associated with an increased risk for ischemic heart disease, atherosclerosis, thrombosis, and stroke. Genetic variation in the Lp(a) locus and some other genes related to Lp(a) synthesis and metabolism play a critical role in regulating plasma Lp(a) levels. The pathophysiological potential of Lp(a) is related to proatherogenic and prothrombotic effects on the vasculature. Different molecular mechanisms underlying the atherothrombotic potential of Lp(a), free apolipoprotein(a), and oxidized-Lp(a) have been proposed. However, plasma Lp(a) assay is complicated by problems associated with quantification and standardization owing to the polymorphic nature of this lipoprotein. This review has focused on the physicochemical properties of Lp(a), the genetic aspects of Lp(a), the need for accurate determination of Lp(a), the synthesis, and recent findings on metabolism of Lp(a). Lastly, the patho-physiological mechanisms by which Lp(a) may increase athero-thrombosis and an overview on the therapeutic modalities to interfere with Lp(a) are summarized.

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Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease?

Cited by 192 publications

References 144 publications

Characteristics, risk factors and treatment reality in livedoid vasculopathy – a multicentre analysis

Characteristics, risk factors and treatment reality in livedoid vasculopathy – a multicentre analysis

Structure, function, and genetics of lipoprotein (a)

Lipoprotein(a): A missing culprit in the management of athero‐thrombosis?

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