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Biomedical subjects

J Hartwich

Publications and source records attributed to J Hartwich.

At least 19 recordsLinked to original sources
PubMed2004

Proangiogenic activity of beta-carotene is coupled with the activation of endothelial cell chemotaxis.

Endothelial cells play an important role in angiogenesis (formation of new vessels from preexisting ones), which is essential for organogenesis, tissue remodeling but also inflammatory response, carcinogenesis in all periods of our life. Beta-carotene (BC) in non-toxic concentrations (up to 3 microM) had no detectable effect on HUVECs (human umbilical vein endothelial cells) proliferation or apoptosis, despite significant changes of the expression patterns of pro- and anti-apoptotic genes. However beta-carotene did not change the tubulogenic activity of HUVEC in the in vitro angiogenesis model, it potently accelerated the bFGF-induced development of microcapillaries, as well as the migration of endothelial cells, in matrigel plug injected subcutaneously to mice. Potent activation of endothelial cell migration in the in vitro model of chemotaxis was also observed. According to the microarray data, genes involved in cell/cell and cell/matrix adhesion, matrix reorganization, activation of chemotaxis, the G-protein regulated intracellular signaling as well as genes involved in the rapid remodeling of protein cytoskeleton were the most affected by BC in HUVEC. We conclude that beta-carotene in the physiological concentration range stimulates early steps of angiogenesis by the activation of cellular migration as well as matrix reorganization and decrease of cell adhesion.

Angiogenesis Inducing Agents↗
PubMed2001

[Is atherosclerosis an autoimmunological process?].

The theories formulated to explain atherogenesis evolved from simple vessel wall lipid accumulation assumption to endothelial dysfunction with adverse vascular wall remodelling hypothesis. The theory that has been accepted lately integrates the former hypotheses and allows for introducing the local immunological activation concept. This immunological activation is initiated by negatively charged and oxidatively modified lipids (e.g. oxPAPC) and their complexes with proteins (like beta 2-GP I). Antibodies and cellular response against chaperonins: HSP 60 and their analogues from bacterial pathogens such as HSP 65, GroEi etc.) as well as release of cytokines, adhesion molecules and inflammatory mediators (CD 40/CD 40-L, IL 15, IFN gamma, IL 1 beta, TNF alpha) also take part in the process. Another important element of atherogenesis is the pathological angiogenic response within the plaque connected with the expression of angiogenic growth factors (such as VEGF, bFGF and PDGF), metallo-proteinases and local hemostasis regulators. This complex activation of local inflammatory and immunological process initiates such phenomena as development of unstable plaque, vascular remodelling, vessel lumen constriction and ischemic, thromboembolic complications of atherosclerosis.

Animals↗
PubMed2000

[Familial LCAT deficiency--clinical picture. Case report].

We report a case of familial LCAT deficiency, diagnosed in a 35 year old women. The disease manifested itself by a presence of proteinuria, corneal opacities and haemolytic anaemia with target cells. Suspecion of familial LCAT deficiency was based on renal biopsy, which revealed characteristic serpiginous fibrillar deposits in electron microscopy. The diagnosis was confirmed by a marked decrease of estrified cholesterol, low HDL-cholesterol concentration, decrease of LCAT activity in serum, typical "stacked coins" picture of HDL lipoproteins in electron microscopy examination and positive familial history--diagnosis of LCAT deficiency in dialysed brother of patient.

Adult↗
PubMed1999

Oxidized low density lipoprotein inhibits inducible nitric oxide synthase, GTP cyclohydrolase I and transforming growth factor beta gene expression in rat macrophages.

Several studies have already demonstrated that oxidized- LDL decreases nitric oxide (NO) generation by cytokine-stimulated macrophages. However, the mechanisms of such an inhibition have not been yet elucidated. NO generation by inducible nitric oxide synthase (iNOS) is dependent on the presence of cofactors for NO generation, tetrathydrobiopterin (BH4) among them. The NO generation by these cells is also regulated by some endogenous inhibitors, like TGF-beta. Therefore, the aim of our recent study was to investigate the influence of ox-LDL on the expression of iNOS and GTP cyclohydrolase I (GTP-CH I), the key enzyme involved in the BH4 synthesis as well as the ox-LDL effect on TGF-beta expression in rat macrophages stimulated with IFNgamma (250 U/ml) and LPS (500 ng/ml). Macrophages, activated in this way, express iNOS, GTP-CH I, and TGF-beta mRNA. This expression was inhibited when the macrophages were preincubated for 24 hours with ox-LDL (100 microg/ml). Quantitative PCR revealed about 10-fold inhibition of iNOS gene expression by ox-LDL. As a consequence of down-regulation of iNOS and GTP-CH I genes, almost 3-fold diminished generation of NO2- by rat macrophages was observed. An inhibition of the TGFbeta mRNA expression was also found. Our studies indicate that decreased NO generation by ox-LDL treated macrophages may be the result of the diminished expression of both iNOS and GTP-CH I genes. This effect may be mediated by the activity of certain endogenous inhibitors of gene expression, however, our studies exclude the TGF-beta as a candidate for this activity.

Animals↗
PubMed1998

Apo E isoforms, insulin output and plasma lipid levels in essential hypertension.

BACKGROUND: The association between apo E isoforms and insulin output during the oral glucose test (OGTT) in 60 non-diabetic, non-obese patients with essential hypertension and in control subjects (non-obese, non-diabetic normotensive subjects) was estimated. METHODS: According to low or high insulin output during OGTT, the subjects were divided into the following groups: normotensive subjects with low (NLI) and high (NHI) and hypertensive subjects with low (HLI) and high (HHI) insulin output. RESULTS: The apo E 4/2 phenotype was detected in 32% of hypertensive subjects but not in control subjects. The frequency of apo E 3/2 phenotype in hypertensive subjects was 5% and in normotensive subjects 15%. An increased frequency of phenotype apo E 4/3 was noticed both in HHI (46%) and in NHI (50%) compared with HLI (22%) and NLI (17%) groups. CONCLUSION: The results suggest that the determination of phenotypes apo E and insulin output may contribute to an early detection of individuals at high risk of hypertension development.

Adult↗
PubMed1997

Regulation of inducible nitric oxide synthase (iNOS) and GTP cyclohydrolase I (GTP-CH I) gene expression by ox-LDL in rat vascular smooth muscle cells.

The generation of nitric oxide is regulated by several factors, including the substrates and cofactors supplementation. Decreased expression and activity of nitric oxide synthase as well as diminished amount of L-arginine or enzyme cofactors results in the inhibition of nitric oxide generation in vascular wall cells. GTP cyclohydrolase 1 is a key enzyme involved in the synthesis of tetrahydrobiopterin, one of the most important cofactors of NO synthases. We have demonstrated that oxidized LDL inhibit not only inducible nitric oxide synthase gene expression but also GTP cyclohydrolase I gene expression in interleukin-1 beta activated rat vascular smooth muscle cells in vitro. It is postulated that diminished availability of tetrahydrobiopterin may additionally impair the generation of nitric oxide in atherosclerosis.

Animals↗
PubMed1996

Heterogeneity of high-density lipoprotein particles and insulin output during oral glucose tolerance test in men with coronary artery disease.

We compared the high-density lipoprotein (HDL) composition and particle heterogeneity in 60 nonobese (normal body mass index, BMI) men suffering from coronary artery disease (CAD) with normolipemia and normoinsulinemia with lower and higher insulin output during the oral glucose tolerance test (silent hyperinsulinemia). The apolipoprotein apoAI, apoAII, and apoE levels were higher in the high insulin response (HI) group than in low insulin response (LI) group. The ratio of apoAI versus total protein and the ratio of apoAI versus total cholesterol were increased in HI compared with LI. The lipid components in HDL were higher in LI than in HI, while for HDL2 they were higher in HI. The fractioning of HDL by gradient gel electrophoresis revealed a different pattern of HDL particles in both groups. The larger particles, HDL2b and HDL2a (mean particle diameters 10.6 and 9.2 nm, respectively), occur more frequently in HI patients (up to 60%) than in LI patients, whereas the smaller particles, HDL3a and HDL3b (mean particle diameters 8.6 and 7.8 nm, respectively), predominate in LI patients. Our results demonstrate that even in the normoglycemic, normocholesterolemic CAD patients, a high insulin output observed during the oral glucose tolerance test may be connected with a different HDL particle pattern, which suggests changes in the reverse cholesterol transport.

Apolipoprotein A-I↗
PubMed1995

A neutrophil-derived NO-synthase (NOS) inhibitor.

In the present work we have demonstrated that the low NOS activity of circulating blood neutrophils is related to an endogenous inhibitory factor. This factor inhibits constitutive NOS (cNOS) of cerebellum and inducible NOS (iNOS) of macrophages in a concentration-dependent manner. Boiling only partially diminished its activity. The inhibition of cNOS was specific, since to some degree NADPH (0.5-4 mM) and more effectively L-arginine (0.1-1 mM), but not D-arginine, reversed the inhibition.

Amino Acid Oxidoreductases↗
PubMed1995

Relation between insulinaemia and lipoprotein composition in men with primary arterial hypertension with and without hypertriglyceridaemia.

The purpose of the study was to evaluate a relationship between HDL, triglyceride levels and insulinaemia in primary arterial hypertension. The study population consisted of 60 men aged 32-68 years (mean age 50.87 years, s.d. 8.4) with hypertension duration of 11.1 years (s.d. 6.4 years) who were compared with 60 normotensives matched for sex, age and BMI. We examined blood pressure, plasma lipoprotein content, sum of glucose and sum of insulinaemia (sum ins) during OGTT (oral glucose tolerance test). OGTT revealed insulin secretion almost twice as high in hypertensives (P < 0.001 sum ins 11002 microU min/ml, s.d. 4846) than in normotensives (sum ins 6662 microU min/ml, s.d. 3099). Comparison of concentration of selected VLDL components shows that hypertensives were characterised by markedly higher concentration of triglycerides (1.46 mmol/L, s.d. 0.87 in hypertensives and 1.04 mmol/L, s.d. 0.54 in normotensives), free and esterified cholesterol and protein, including apolipoprotein B than normotensives. It was also found that hypertensives had higher levels of apo CIII0 and lower levels of CIII1 VLDL than normotensives. Hypertensive patients showed also a higher frequency of apo E2 isoforms (three-fold) and apo E4 isoforms (two-fold) than healthy subjects. No changes were detected in the composition of LDL and HDL between the groups. Analysing the discriminating ability of biochemical parameters chosen in a step-wise manner it was found that sum ins and HDL, protein and cholesterol concentrations were the factors most powerfully differentiating men with hypertension from healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Modulation of LDL catabolism by sodium nitroprusside and PGE2 in human peripheral blood lymphocytes.

The effect of nitric oxide donor--sodium nitroprusside (NaNP) and PGE2 on the LDL-receptor activity and LDL cellular accumulation by isolated human blood lymphocytes was investigated. Preincubation of lymphocytes with lipoprotein deficient medium (LPDS) resulted in the increase of the LDL-receptor activity and the LDL-cellular accumulation. NaNP (30-300 microM) dose-dependently prevented the increase of the LDL-receptor activity as well as the accumulation of LDL by lymphocytes. However, in "starwing" cells (cells with high LDL-receptor activity) the effect of NaNP on the receptor activity was biphasic. At concentration up to 100 microM NaNP inhibited, while at a concentration of 300 microM, it activated the LDL-receptor activity. PGE2 (3-30 microM) inhibited LDL catabolism, however, this effect was hardly concentration-dependent.

Dinoprostone↗
PubMed1993

[Decrease in the level of free cholesterol fraction HDL as a risk factor for threatened atherosclerosis in idiopathic hyperinsulinemia].

Inversive association between concentration of plasma high density lipoprotein (HDL) components and endogenous insulin response to oral glucose uptake was observed in 89 healthy, normolipidaemic, non obese, non diabetic male subjects. Inversive correlation between sum of insulin released during oral glucose tolerance test and HDL free and esterified cholesterol as well as apolipoprotein A1 concentration were confirmed. Coexistence of increased insulin secretion and low ratio of free cholesterol concentration to esterified cholesterol and to proteins in HDL was also observed. In separate group of subjects with normal glucose tolerance in high insulin response subgroup the cholesterol (free and esterified) and protein concentrations were lower than in subgroup with low insulin response. The free cholesterol/esterified cholesterol and free cholesterol/protein (apoA1) ratios were decreased in high insulin response subgroup. It is concluded that low concentration of free cholesterol is a most significant change of HDL composition in hyperinsulinemic, healthy men.

Adult↗
PubMed1989

Incides of lipid peroxidation in patients with hypercholesterolemia and hypertriglyceridemia.

Peroxidation of lipoproteins has received attention recently in connection with its possible initiation and propagation of atherosclerosis. We studied indices of lipid peroxidation in plasma of 30 patients with either hypercholesterolemia or both hypercholesterolemia and hypertriglyceridemia, and compared them with those of 19 healthy subjects. In the patients lipid hydroperoxides measured both iodometrically and as thiobarbituric acid-reactive substances (TBA-RS) were significantly increased, while concentrations of thiol groups remained unchanged. There was no correlation between concentrations of hydroperoxides and TBA-RS, possibly because the two methods assessed different breakdown products of lipid peroxidation. Lipid hydroperoxide levels, but not those of TBA-RS were correlated with LDL-cholesterol and triglyceride levels. In 6 patients administration of vitamin E at a daily dosage of 300 mg for 4 to 6 weeks depressed elevated hydroperoxides by 33%, and TBA-RS by 44% on average.

Adult↗
PubMed1981

Serum lipoproteins, lipid peroxides and prostacyclin biosynthesis in patients with coronary heart disease.

Serum low-density lipoproteins (LDL) and high-density lipoproteins (HDL) were prepared by gradient ultracentrifugation and dialysis from 12 healthy subjects and 15 patients with coronary heart disease and hyperlipoproteinemia. In both lipoprotein fractions cholesterol and lipid peroxides were determined. The effect of these lipoproteins on spontaneous prostacyclin biosynthesis in rat aortic slices was studied. Serum lipoproteins were susceptible to peroxidation during the preparation procedure. LDL were more prone to peroxidation than HDL. Little lipid peroxides were formed in lipoproteins when calcium ions had been removed by EDTA, and when butylated hydroxytoluene (BHT) was present at all stages of their preparation. LDL when prepared without these precautions either from healthy subjects or from patients with coronary heart disease markedly suppressed prostacyclin generation by rat aortic slices. This inhibition was unrelated to LDL-cholesterol, but was due to LDL-lipid peroxides. Peroxide-low LDL prepared from most of the healthy subjects and patients with coronary heart disease and concomitant hyperlipoproteinemia, did not inhibit prostacyclin biosynthesis. However, in one quarter of the patients, LDL was inhibitory. Consequently, in some patients with coronary heart disease, there operate unknown mechanisms which are responsible for the inhibitory activity of LDL on prostacyclin generation.

Adult↗