A Low-Molecular-Weight Phenotype of Apolipoprotein(a) as a Factor Provoking Accumulation of Cholesterol by THP-1 Monocyte-Like Cells

Афанасьева, О. И.; Vikhrova, E. B.; Utkina, E.; Афанасьева, М. И.; Klesareva, E.; Radyukhina, N. V.; Aref'eva, T I; Pokrovsky, S.

doi:10.1007/s10517-019-04452-w

Cited by 2 publications

(2 citation statements)

References 12 publications

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“…The presence of apo(a) in atherosclerotic vascular lesions from the lipid band to plaque rupture, as well as its presence in the macrophage-enriched area, has been demonstrated in morphological and immunohistochemical studies [ 60 , 61 ]. Previously, our in vitro studies showed that THP-1 macrophage cells accumulate cholesterol much more actively when adding serum from patients with the LMW apo(a) phenotype, regardless of the content of other lipids and the initial concentration of Lp(a) [ 62 ]. Thus, one of the pathophysiological mechanisms of the greater “atherothrombogenicity” of the LMW apo(a) phenotype may be its ability to activate immune cells to a greater extent, thereby increasing and maintaining inflammation in the atherosclerotic plaque, making it more vulnerable.…”

Section: Discussionmentioning

confidence: 99%

Lipoprotein(a) and Low-Molecular-Weight Apo(a) Phenotype as Determinants of New Cardiovascular Events in Patients with Premature Coronary Heart Disease

Afanasieva,

Tyurina,

Ezhov

et al. 2023

Diseases

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Background. Lipoprotein(a) (Lp(a)) is a genetic risk factor of atherosclerotic cardiovascular diseases (ASCVDs). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is related to vascular inflammation and detected in atherosclerotic plaques. A temporary increase in the circulating concentration of PCSK9 and Lp(a) was shown in patients with myocardial infarction (MI). The aim of this study was to evaluate the role of the apo(a) phenotype and the Lp(a) concentration as well as its complex with PCSK9 in the development of cardiac events and MI in patients with a premature manifestation of coronary heart disease (CHD). Methods. In a prospective study with retrospective data collection, we included 116 patients with premature CHD who were followed for a median of 14 years. The medical history and information on cardiovascular events after an initial exam as well as data on the levels of lipids, Lp(a), PCSK9, PCSK9-Lp(a) complex, and apo(a) phenotype were obtained. Results. The patients were divided into two groups depending on the presence of a low- (LMW, n = 52) or high-molecular weight (HMW, n = 64) apo(a) phenotype. LMW apo(a) phenotype (odds ratio 2.3 (1.1 to 4.8), p = 0.03), but not elevated Lp(a) (1.9 (0.8–4.6), p = 0.13), was an independent predictor for the development of MI after adjustment for sex, age of CHD debut, initial lipids levels, and lipid-lowering treatment. The apo(a) phenotype also determined the relationship between Lp(a) and PCSK9 concentrations. The level of the PCSK9-Lp(a) complex was higher in LMW apo(a) patients. Conclusion. The LMW apo(a) phenotype is a risk factor for non-fatal MI in a long-term prospective follow-up of patients with premature CHD, and this link could be mediated via PCSK9.

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Section: Discussionmentioning

confidence: 99%

Lipoprotein(a) and Low-Molecular-Weight Apo(a) Phenotype as Determinants of New Cardiovascular Events in Patients with Premature Coronary Heart Disease

Afanasieva,

Tyurina,

Ezhov

et al. 2023

Diseases

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“…The incubation of the serum samples from patients with LMW apo(a) phenotype causes a significantly greater accumulation of cholesterol by macrophage cells of THP-1, compared with serum samples from patients with HMW apo(a) phenotype, regardless of Lp(a) concentration ( 31 ) and this observation may be related to the difference in Lp(a) particles atherogenicity.…”

Section: Discussionmentioning

confidence: 99%

Low Molecular Weight Apolipoprotein(a) Phenotype Rather Than Lipoprotein(a) Is Associated With Coronary Atherosclerosis and Myocardial Infarction

Afanasieva

Ezhov

Tmoyan

et al. 2022

Front. Cardiovasc. Med.

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Background and AimsCurrent evidence suggests that lipoprotein(a) [Lp(a)] level above 50 mg/dL is associated with increased cardiovascular risk. Our study aim was to determine the relationship of apolipoprotein(a) [apo(a)] phenotypes and Lp(a) concentration below and above 50 mg/dL with coronary atherosclerosis severity and myocardial infarction (MI).Material and MethodsThe study population consisted of 540 patients (mean age 54.0 ± 8.8 years, 82% men) who passed through coronary angiography. The number of diseased major coronary arteries assessed atherosclerosis severity. Lipids, glucose, Lp(a) levels and apo(a) phenotypes were determined in all patients. All patients were divided into four groups: with Lp(a) <50 mg/dL [ “normal” Lp(a)] or ≥50 mg/dL [hyperLp(a)], and with low-molecular (LMW) or high-molecular weight (HMW) apo(a) phenotypes.ResultsBaseline clinical and biochemical characteristics were similar between the groups. In groups with LMW apo(a) phenotypes, the odds ratio (OR; 95% confidence interval) of multivessel disease was higher [10.1; 3.1–33.5, p < 0.005 for hyperLp(a) and 2.2; 1.0–4.9, p = 0.056 for normal Lp(a)], but not in the group with HMW apo(a) and hyperLp(a) [1.1; 0.3–3.3, p = 0.92] compared with the reference group with HMW apo(a) and normal Lp(a). Similarly, MI was observed more often in patients with LMW apo(a) phenotype and hyperLp(a) and normal Lp(a) than in groups with HMW apo(a) phenotype.ConclusionThe LMW apo(a) phenotype is associated with the severity of coronary atherosclerosis and MI even when Lp(a) level is below 50 mg/dL. The combination of Lp(a) level above 50 mg/dL and LMW apo(a) phenotype increases the risk of severe coronary atherosclerosis, regardless of other risk factors.

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A Low-Molecular-Weight Phenotype of Apolipoprotein(a) as a Factor Provoking Accumulation of Cholesterol by THP-1 Monocyte-Like Cells

Cited by 2 publications

References 12 publications

Lipoprotein(a) and Low-Molecular-Weight Apo(a) Phenotype as Determinants of New Cardiovascular Events in Patients with Premature Coronary Heart Disease

Lipoprotein(a) and Low-Molecular-Weight Apo(a) Phenotype as Determinants of New Cardiovascular Events in Patients with Premature Coronary Heart Disease

Low Molecular Weight Apolipoprotein(a) Phenotype Rather Than Lipoprotein(a) Is Associated With Coronary Atherosclerosis and Myocardial Infarction

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