Plasma lipoprotein(a) concentration as an independent predictor of hemodynamic progression of aortic valve stenosis

Alexandrova, Margarita L.; Atanasova, Milena; Tzekova, M.; Rashev, Tihomir R.; Ahmad, Sarfraz

doi:10.1007/s11010-020-03797-5

Cited by 6 publications

(5 citation statements)

References 38 publications

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“…factor, lost part of its initial independent predictive value. In a previous study, TG levels were associated with calcific AS (26); however, patients in the high FSTL1 cohort were associated with high TG levels in our cohort. We speculated that FSTL1 might also partly attenuate the pro-calcification properties of lipid disorders.…”

Section: Discussioncontrasting

confidence: 77%

Role of follistatin-like 1 levels and functions in calcific aortic stenosis

Zhang

Gao

et al. 2023

Front. Cardiovasc. Med.

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BackgroundCalcific aortic valve disease (CAVD) is a progressive disease resulting in severe calcific aortic stenosis (AS), and there is increasing interest in the discovery of novel biomarkers to identify patients with potential future calcific AS at an early stage. This study aimed to determine whether follistatin-like 1 (FSTL1) is associated with calcific AS events and its exact role in aortic valve calcification.MethodsA prospective observational cohort study involving 656 patients was performed to investigate the relationship between serum FSTL1 and calcific AS incidence during a follow-up of 5 years. Furthermore, we detected FSTL1 levels in valvular interstitial cells (VICs) from calcified valves and explored the effects of FSTL1 on VIC osteogenic differentiation in vitro as well as the signaling pathways involved.ResultsDuring a median follow-up of 5 years, lower FSTL1 levels were associated with a significantly higher risk of calcific AS events (log rank test, P = 0.007). In addition, Cox multivariable regression analyses verified the predictive value of FSTL1 after adjusting for both demographic features and laboratory confounders. Consistent with our results for serum, a lower concentration of FSTL1 was observed in calcified human valves (n = 11) and mainly colocalized with VICs. Recombinant human FSTL1 (rhFSTL1) stimulation inhibited calcium deposition, alkaline phosphatase (ALP) activity, and osteogenic gene expression partly through the downregulation of the ERK1/2 pathway.ConclusionTaken together, this study provides a strong rationale to consider FSTL1 as a potential therapeutic target for calcific AS.

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Section: Discussioncontrasting

confidence: 77%

Role of follistatin-like 1 levels and functions in calcific aortic stenosis

Zhang

Gao

et al. 2023

Front. Cardiovasc. Med.

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“…The assembly of LpA remains an enigma, involving a series of intricate noncovalent interactions followed by the formation of a crucial disulfide bond [49,50]. Nevertheless, an inverse correlation is observed between plasma LpA levels and ApoA isoform size, primarily attributed to the constant production of ApoA in the liver, with smaller isoforms being generated more prolifically than larger ones [51]. Despite extensive research, the clearance pathways for LpA remain largely elusive, although LDLR-, VLDLR-, CD36-, and SR-B1-mediated hepatic clearance and proteolytic cleavage may play a role [52].…”

Section: Apolipoproteinmentioning

confidence: 99%

Intracranial Aneurysms and Lipid Metabolism Disorders: From Molecular Mechanisms to Clinical Implications

Pan,

Shi,

et al. 2023

Biomolecules

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Many vascular diseases are linked to lipid metabolism disorders, which cause lipid accumulation and peroxidation in the vascular wall. These processes lead to degenerative changes in the vessel, such as phenotypic transformation of smooth muscle cells and dysfunction and apoptosis of endothelial cells. In intracranial aneurysms, the coexistence of lipid plaques is often observed, indicating localized lipid metabolism disorders. These disorders may impair the function of the vascular wall or result from it. We summarize the literature on the relationship between lipid metabolism disorders and intracranial aneurysms below.

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“…75 It also seems that increased Lp(a) and OxPL contribute to progression of the disease and may thus be targeted for treatment. 76,77 Accumulating evidence suggests that Lp(a) can accentuate pathophysiological processes in AS, particularly, endothelial dysfunction, foam cell formation, and enhancing a proinflammatory state. 78 The proinflammatory effects of Lp(a) lead to valve thickening and mineralization via pro-osteogenic signaling and alterations in gene expression in valve interstitial cells that is mainly enhanced by the content of Lp(a) in OxPL.…”

Section: Aortic Valve Calcification and Stenosis (As)mentioning

confidence: 99%

Lipoprotein(a) and Cardiovascular Disease: A Missing Link for Premature Atherosclerotic Heart Disease and/or Residual Risk

Melita

Manolis

Manolis³

et al. 2022

Journal of Cardiovascular Pharmacology

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Lipoprotein(a) or lipoprotein "little a" [Lp(a)] is an under-recognized causal risk factor for cardiovascular (CV) disease (CVD), including coronary atherosclerosis, aortic valvular stenosis, ischemic stroke, heart failure, and peripheral arterial disease. Elevated plasma Lp(a) ($50 mg/dL or $100 nmol/L) is commonly encountered in almost 1 in 5 individuals and confers a higher CV risk compared with those with normal Lp(a) levels, although such normal levels have not been generally agreed upon. Elevated Lp(a) is considered a cause of premature and accelerated atherosclerotic CVD. Thus, in patients with a positive family or personal history of premature coronary artery disease (CAD), Lp(a) should be measured. However, elevated Lp(a) may confer increased risk for incident CAD even in the absence of a family history of CAD, and even in those who have guideline-lowered LDL cholesterol (,70 mg/dL) and continue to have a persisting CV residual risk. Thus, measurement of Lp(a) will have a significant clinical impact on the assessment of atherosclerotic CVD risk, and will assume a more important role in managing patients with CVD with the advent and clinical application of specific Lp(a)-lowering therapies. Conventional therapeutic approaches like lifestyle modification and statin therapy remain ineffective at lowering Lp(a). Newer treatment modalities, such as gene silencing via RNA interference with use of antisense oligonucleotide(s) or small interfering RNA molecules targeting Lp(a), seem very promising. These issues are herein reviewed, accumulated data are scrutinized, metaanalyses and current guidelines are tabulated, and Lp(a)related CVDs and newer therapeutic modalities are pictorially illustrated.

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Plasma lipoprotein(a) concentration as an independent predictor of hemodynamic progression of aortic valve stenosis

Cited by 6 publications

References 38 publications

Role of follistatin-like 1 levels and functions in calcific aortic stenosis

Role of follistatin-like 1 levels and functions in calcific aortic stenosis

Intracranial Aneurysms and Lipid Metabolism Disorders: From Molecular Mechanisms to Clinical Implications

Lipoprotein(a) and Cardiovascular Disease: A Missing Link for Premature Atherosclerotic Heart Disease and/or Residual Risk

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