Hyperhomocysteinemia, lipid and lipoprotein disturbances in patients with primary hypertension

Baszczuk, Aleksandra; Musialik, Katarzyna; Kopczyński, J; Thielemann, Anna; Kopczyński, Zygmunt; Kęsy, Lena; Dopierała, Gabriela

doi:10.1016/j.advms.2013.08.001

Cited by 24 publications

(13 citation statements)

References 32 publications

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“…Importantly, a correlation between serum hcy levels and lipids and lipoproteins has been observed [36]. A high concentration of LDL is found in patients with hhcy and primary hypertension, coupled to enhanced secretion of VLDL triglycerides [37]. VLDLs and LDLs are considered as one of the most important pro-atherogenic factors, and APO E is a major component of these particles.…”

Section: Discussionmentioning

confidence: 98%

Corrective effects of hepatotoxicity by hepatic Dyrk1a gene delivery in mice with intermediate hyperhomocysteinemia

Latour

Salameh

Carbonne

et al. 2015

Molecular Genetics and Metabolism Reports

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Hyperhomocysteinemia results from hepatic metabolism dysfunction and is characterized by a high plasma homocysteine level, which is also an independent risk factor for cardiovascular disease. Elevated levels of homocysteine in plasma lead to hepatic lesions and abnormal lipid metabolism. Therefore, lowering homocysteine levels might offer therapeutic benefits. Recently, we were able to lower plasma homocysteine levels in mice with moderate hyperhomocysteinemia using an adenoviral construct designed to restrict the expression of DYRK1A, a serine/threonine kinase involved in methionine metabolism (and therefore homocysteine production), to hepatocytes. Here, we aimed to extend our previous findings by analyzing the effect of hepatocyte-specific Dyrk1a gene transfer on intermediate hyperhomocysteinemia and its associated hepatic toxicity and liver dysfunction. Commensurate with decreased plasma homocysteine and alanine aminotransferase levels, targeted hepatic expression of DYRK1A in mice with intermediate hyperhomocysteinemia resulted in elevated plasma paraoxonase-1 and lecithin:cholesterol acyltransferase activities and apolipoprotein A–I levels. It also rescued hepatic apolipoprotein E, J, and D levels. Further, Akt/GSK3/cyclin D1 signaling pathways in the liver of treated mice were altered, which may help prevent homocysteine-induced cell cycle dysfunction. DYRK1A gene therapy could be useful in the treatment of hyperhomocysteinemia in populations, such as end-stage renal disease patients, who are unresponsive to B-complex vitamin therapy.

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Section: Discussionmentioning

confidence: 98%

Corrective effects of hepatotoxicity by hepatic Dyrk1a gene delivery in mice with intermediate hyperhomocysteinemia

Latour

Salameh

Carbonne

et al. 2015

Molecular Genetics and Metabolism Reports

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“…An increase in HDL-cholesterol concentration may be an indirect effect of the reduction of the homocysteine concentration by folic acid. The administration of folic acid influences the efficiency of the process of remethylation of homocysteine to methionine (1).…”

Section: Discussionmentioning

confidence: 99%

“…5-Metylotetrahydropholian prevents oxidation, stabilizes and regenerates tetrahydrobiopterin BH4, which is a cofactor necessary in the reaction of the release of nitric oxide catalyzed by endothelium synthase eNOS lowering the concentration of homocysteine (30). Moreover, the lowering of the level of homocysteine in patients after the administration of folic acid can overcome adverse effects of hyperhomocysteinaemia, such as the increase of oxide stress and lowering of the bioavailability of nitric oxide (1,2).…”

Section: Discussionmentioning

confidence: 99%

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The Impact of Supplementation with Folic Acid on Homocysteine Concentration and Selected Lipoprotein Parameters in Patients with Primary Hypertension

Baszczuk¹,

Thielemann²,

Musialik³

et al. 2017

J Nutr Sci Vitaminol

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SummaryThe aim of the study was the assessment of the impact of supplementation with folic acid on the concentration of homocysteine, total cholesterol (TC), HDL-and LDLcholesterol, triglycerides (TG), apoprotein AI (apoAI) and apoprotein B (apoB) in patients suffering from primary hypertension. The examined group comprised 42 patients suffering from primary hypertension. All examined patients underwent laboratory tests as follows: concentration of homocysteine, folic acid, TC, LDL-cholesterol, HDL-cholesterol, TG, apoAI and apoB. All patients were orally administered with 15 mg of folic acid per day for 45 d. After this period, all laboratory tests were repeated. Homocysteine concentration was measured by the FPIA method, concentrations of apoAI and apoB were measured by the nephelometric method, and other parameters with routine methods. After administration of 15 mg of folic acid to patients with primary hypertension, a considerable decrease in the concentration of homocysteine was observed in parallel with a substantive growth of HDLcholesterol, as well as apoprotein AI concentrations and a reduction of the apoprotein B concentration. Results of statistical analysis indicated a significant correlation between the decline in homocysteine concentration and the increase in HDL-cholesterol concentration, as well as between the increase of folic acid concentration and the increase in apoAI concentration in patients following the intake of folic acid. The drop in homocysteine concentration through the supplementation with folic acid can cause quantitative changes in the lipid and lipoprotein parameters which, in consequence, may lead to the mitigation of risk concerning the development of atherosclerosis. Key Words hypertension, hyperhomocysteinaemia, cholesterol, triglycerides, apoproteins Hypertension is one of the most common symptoms of cardiovascular diseases. Ninety percent of affected patients are diagnosed with primary hypertension. The etiology of this disease includes numerous genetic, environmental and neuro-hormonal factors, which often co-exist and are linked one to another. Due to that fact, hypertension is frequently accompanied by metabolic disorders such as obesity, diabetes, and hyperlipidaemia. These diseases are often also accompanied by mild chronic inflammation, disorders of the coagulation system and fibrinolysis, as well as hyperhomocysteinaemia. Some of the cardiovascular disease risk factors may be modified through a change in lifestyle and medication. The positive impact of modified standard risk factors, such as disturbances in lipid and carbohydrate metabolism disorders, as well as obesity, is relatively well documented.As far as hyperhomocysteinaemia is concerned, studies on its importance in the development of hypertension, as well as on the impact of its treatment in eliminating the risk of cardiovascular diseases, are still being carried out. High blood pressure is often accompanied by hyperhomocysteinaemia. High level of homocysteine could adversely affect the synthesis and bioacc...

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“…Concerning the inflammatory markers beta-2 microglobulin [4] and homocysteine [5], there are not enough studies that correlate these markers with aldosterone and resistant hypertension; nevertheless, it is a known fact that they are both present in patients with cardiovascular risk. Beta-2 microglobulin is a low molecular weight protein associated with class I major histocompatibility complex (MHC-I) proteins.…”

Section: Introductionmentioning

confidence: 99%

Serum Aldosterone Levels In Hypertension

Rigolo¹,

Meneghini²,

Murad³

et al. 2016

Int Arch Med

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Aims: Hypertension affects around 30% of the adult population. It is related to cardiovascular complications, especially on account of atherosclerosis. Resistant hypertension (RH) occurs when blood pressure remains above target value despite the use of three antihypertensive medications with synergistic actions at maximum recommended doses or whenever the patient makes use of four or more antihypertensive drugs even when blood pressure is controlled. Hyperaldosteronism is an important cause of RH. The study aims to evaluate the association of aldosterone concentrations not only in essential hypertensive individuals but with RH correlating also with inflammatory levels.Methods: A total of 44 EH patients and 32 RH patients were selected. All of them were submitted to serum analysis of urea, creatinine, potassium, aldosterone, fasting glycemia, glycated hemoglobin (HbA1C), complete blood count, usCRP, homocysteine and beta-2 microglobulin (B2M). Results:No significant difference could be observed among the groups regarding the inflammatory markers TNF-alpha, IL-6, usCRP, homocysteine and B2M. As to aldosterone and the ratio of albumin to creatinine (ACR), there was an expressive difference; however, no correlation between ACR and aldosterone could be found. Conclusions:In this sample of hypertensive individuals, aldosterone levels are relatively higher in RH when compared with those with EH.

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Hyperhomocysteinemia, lipid and lipoprotein disturbances in patients with primary hypertension

Cited by 24 publications

References 32 publications

Corrective effects of hepatotoxicity by hepatic Dyrk1a gene delivery in mice with intermediate hyperhomocysteinemia

Corrective effects of hepatotoxicity by hepatic Dyrk1a gene delivery in mice with intermediate hyperhomocysteinemia

The Impact of Supplementation with Folic Acid on Homocysteine Concentration and Selected Lipoprotein Parameters in Patients with Primary Hypertension

Serum Aldosterone Levels In Hypertension

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