scispace - formally typeset
Search or ask a question
Author

Mircea Cucuianu

Bio: Mircea Cucuianu is an academic researcher from Iuliu Hațieganu University of Medicine and Pharmacy. The author has contributed to research in topics: Proinflammatory cytokine & Thrombomodulin. The author has an hindex of 2, co-authored 7 publications receiving 19 citations.

Papers
More filters
01 Jan 2007
TL;DR: Evidence has been provided that increased levels of non esterified fatty acids in the portal flow would produce insulin resistance and would also stimulate the hepatic protein synthesis, thereby explaining the increased plasma levels not only of apolipoprotein B, but also of other liver-derived enzymes and proteins occurring in overweight and hypertriglyceridemic patients.
Abstract: Evidence has been provided that increased levels of non esterified fatty acids (NEFA) in the portal flow would produce insulin resistance and would also stimulate the hepatic protein synthesis, thereby explaining the increased plasma levels not only of apolipoprotein B, but also of other liver-derived enzymes and proteins occurring in overweight and hypertriglyceridemic patients. The high plasma concentration of triglyceride-rich lipoprotein would facilitate the transfer of cholesteryl esters from HDL and LDL to VLDL in exchange for triglycerides, a process mediated by liver-derived cholesteryl ester transfer protein (CETP). The triglyceride thereby acquired in HDL and LDL would then be hydrolyzed by hepatic lipase. The resulting association of increased triglycerides, low HDL cholesterol and small dense LDL is considered to be an atherogenic profile. The prothrombotic state, another feature of the metabolic syndrome, may also be explained by an enhanced hepatic synthesis of clotting factors and of the inhibitors of fibrinolysis. It was recently shown that adipocyte synthesized adiponectin reduces the release of fatty acids from the adipose tissue and would also enhance their uptake and oxidation in the muscle, thereby limiting their uptake in the liver. Decreased adiponectin production in obesity would therefore promote the development of insulin resistance, of atherogenic dyslipidemia and of the prothrombotic state. Because adiponectin also exerts an antiinflammatory activity by antagonizing TNFalpha, hypoadiponectinemia may be involved in atherogenesis and in the progression of hepatic steatosis to steatohepatitis.

11 citations

Journal ArticleDOI
TL;DR: DNA methylation and histone modifications were shown to be associated with VLDL and LDL phenotypes, with hyperglycemia and reduced level of HDL cholesterol, withhypertriglyceridemic waist phenotype and with progression of atherosclerotic occlusion in peripheral arteries.
Abstract: Abstract Metabolic syndrome is a complex pathology including central obesity, impaired glucose tolerance/diabetes, an atherogenic dyslipidemia and a prothrombotic state. A new perspective on understanding the mechanisms underlying metabolic syndrome is provided by the epigenetic changes (mainly DNA methylation and histone covalent modifications), which influence gene expression without changing of the DNA sequence. DNA methylation (mainly in carnitine palmitoyltransferase 1A gene) and histone modifications were shown to be associated with VLDL and LDL phenotypes, with hyperglycemia and reduced level of HDL cholesterol, with hypertriglyceridemic waist phenotype and with progression of atherosclerotic occlusion in peripheral arteries. The epigenetic changes can occur in the prenatal period, throughout the life span, and can be transmitted to the offspring. Both poor maternal nutrition and maternal obesity, diabetes and overfeeding can result in epigenetic alterations that amplify the risk of metabolic syndrome for the offspring. Throughout life span, environmental factors, such as nutrition and exercise can induce epigenetic changes influencing the evolution of the metabolic syndrome (through adipocyte metabolism and insulin signaling pathway). The epigenetic modifications are not completely erased during gametogenesis and embryogensis, resulting in a transgenerational transmission of an epigenetic state up to the fifth generation. Epigenetic mechanisms are an interface between environmental stimuli and resulting phenotype by inducing a certain transcriptional state, which may be also transmitted to the next generation(s) and which may predispose to an increased risk for developing metabolic syndrome in the context of a mismatched environment. Elucidating epigenetic modulation might provide additional information about risk evaluation and more targeted therapeutical intervention.

9 citations

Journal ArticleDOI
TL;DR: Infusions of activated protein C were reported to protect from a toxico-septic shock by exerting not only anticoagulant but also anti-inflammatory effects.
Abstract: Protein C is a vitamin K-dependent serine protease secreted by the hepatocytes as an inactive zymogen and activated by thrombin bound to endothelial thrombomodulin. An endothelial protein C receptor (EPCR) is involved in both activation and enhancement of protein C activity, resulting in proteolytic degradation of clotting factors Va and VIIIa, thereby providing an efficient anticoagulant mechanism. Evidence was also provided that proinflammatory cytokines would impair the endothelia-mediated activation and activity of the Protein C system by inducing an internalization and proteolytic degradation of thrombomodulin and by shedding EPCR from the surface of endothelial cells membrane. Clinical and experimental studies also emphasized that an inflammatory acute phase reaction is accompanied by a commuted hepatic protein synthesis leading to an increase of plasma fibrinogen, factor VIII:C and of α1 protease inhibitor, while the plasma level of protein C zymogen decrease. On the other hand infusions of activated protein C were reported to protect from a toxico-septic shock by exerting not only anticoagulant but also anti-inflammatory effects.

1 citations

Journal Article
TL;DR: It may be suggested that the decreased lipoprotein lipase noted in atherosclerotic patients is not a major pathogenic link, being rather related to the inflammatory component of the disease, its expression being reduced by proinflammatory cytokines.
Abstract: More than 40 years ago, our laboratory reported that post-heparin lipolytic activity was decreased in patients with severe atherosclerotic disease, while values recorded in obese and hyperlipidemic subjects without clinically detectable atherosclerotic lesions did not significantly differ from normal weight normolipidemic controls Because in 1967 data on pathophysiology of lipolytic enzymes were rather scarce, and mainly because our information facilities were limited in those years, we had difficulties in interpreting these results, and the study was to some extent awkwardly approached, as the investigated subjects were not considered according to their gender, body fat patterning and type of hyperlipoproteinemia, and the lipolytic activities of lipoprotein lipase and hepatic lipase had not been selectively assessed Reviewing recent data in the literature it was noted that pre-heparin lipoprotein lipase mass assessed by ELISA was indeed significantly lower in insulin resistant coronary patients than in patients with no lesions, and correlated negatively with the severity of atherosclerotic lesions Noteworthy hypoadiponectinemia, a hallmark of insulin resistance, was associated with decreased lipoprotein lipase and increased hepatic lipase activities Clustering of increased plasma VLDL-triglyceride, cholesteryl-ester transfer protein and hepatic lipase would remodel HDL and LDL particles, generating an atherogenic lipoprotein profile In opposition to atherogenic dyslipidemia related to an enhanced hepatic secretion of VLDL, cases with important hypertriglyceridemia subsequent to deficient lipolytic clearance are at a rather low risk for coronary artery disease It may therefore be suggested that the decreased lipoprotein lipase noted in atherosclerotic patients is not a major pathogenic link, being rather related to the inflammatory component of the disease, its expression being reduced by proinflammatory cytokines

Cited by
More filters
Journal ArticleDOI
TL;DR: Evaluating hepatic lipase activity in NAFLD patients and its relationship to the severity of hepatic steatosis found it to be related to insulin resistant states.
Abstract: Background and objective Hepatic lipase is a lipolytic enzyme mostly synthesized and localized at the surface of liver sinusoidal capillaries, which hydrolyses triglycerides and phospholipids of intermediate density, large low density (LDL) and high density lipoproteins. Hepatic lipase activity is increased in insulin resistant states. Non-alcoholic fatty liver disease (NAFLD) is characterized by insulin resistance. However, at present, no data are available regarding the behaviour of hepatic lipase with regard to the degree of hepatic steatosis. Our aim was to evaluate hepatic lipase activity in NAFLD patients and its relationship to the severity of hepatic steatosis. Design and patients We studied 48 patients with NAFLD (diagnosed by ultrasonography and confirmed by liver biopsy) and 30 controls. Steatosis was semi-quantitatively assessed and considered as mild or grade 1, moderate or grade 2 and severe or grade 3. Measurements: hepatic lipase activity, lipid and lipoprotein profile (including intermediate density lipoproteins and dense LDL), adiponectin, insulin, glucose and high sensitivity C-reactive protein were measured. Homeostasis model assessment for insulin resistance (HOMA) index was calculated. Results Patients with hepatic steatosis presented with higher hepatic lipase activity, HOMA and dense LDL and lower levels of adiponectin, high density lipoproteins, cholesterol and apoA-I. Hepatic lipase activity positively correlated significantly with the severity of hepatic steatosis. Hepatic lipase correlated with a more atherogenic profile and persisted higher in patients even after corrected for age, gender, body mass index, HOMA and adiponectin. Conclusion The higher hepatic lipase activity in NAFLD patients contributes to a more atherogenic profile linked to increased cardiovascular risk, beyond the insulin resistance and the reduction in adiponectin. Copyright © 2012 John Wiley & Sons, Ltd.

39 citations

Journal Article
TL;DR: Results show that in a population with a genetic tendency for obesity, effects of maternal obesity accumulate over successive generations to shift the population distribution toward increased adult body weight, and suggest that epigenetic mechanisms are involved in this process.
Abstract: Background:The obesity epidemic, recognized in developed nations for decades, is now a worldwide phenomenon. All age groups are affected, including women of childbearing age, fueling concern that maternal obesity before and during pregnancy and lactation impairs developmental establishment of body weight regulatory mechanisms in the fetus or infant, causing transgenerational amplification of obesity prevalence and severity. The biological mechanisms underlying such processes remain unknown.Methods:We used agouti viable yellow (Avy) mice to test the hypothesis that maternal obesity induces transgenerational amplification of obesity. We passed the Avy allele through three generations of Avy/a females and assessed cumulative effects on coat color and body weight. By studying two separate but contemporaneous populations of mice, one provided a standard diet and the other a methyl-supplemented diet that induces DNA hypermethylation during development, we tested whether potential transgenerational effects on body weight might be mediated by alterations in epigenetic mechanisms including DNA methylation.Results:The genetic tendency for obesity in Avy mice was progressively exacerbated when the Avy allele was passed through successive generations of obese Avy females. This transgenerational amplification of body weight was prevented by a promethylation dietary supplement. Importantly, the effect of methyl supplementation on body weight was independent of epigenetic changes at the Avy locus, indicating this model may have direct relevance to human transgenerational obesity.Conclusion:Our results show that in a population with a genetic tendency for obesity, effects of maternal obesity accumulate over successive generations to shift the population distribution toward increased adult body weight, and suggest that epigenetic mechanisms are involved in this process.

30 citations

M Cucuianu1, Mariana Coca
01 Apr 2012
TL;DR: Investigations and data in the literature suggest impaired fibrinolysis in overweight hypertriglyceridemic subjects are mainly due to increased plasma levels of coagulation factor XIII and PAI-1, and anticoagulant plasma proteins C and S levels were found to be increased in overweight and hyperlipidemic patients considered to be at risk for thrombotic complications.
Abstract: Studies initiated 30 years ago emphasized that dilute blood clot lysis time was longer in obese diabetic patients than in normal weight diabetics. It was also later reported that when compared to obese women with gluteal and femoral adiposity, the age matched men with abdominal obesity displayed a more delayed clot lysis, higher triglyceride levels and higher cholinesterase activity, as well as more increased concentration of plasminogen activator inhibitor-1 (PAL-1). According to authors' investigations and data in the literature, impaired fibrinolysis in overweight hypertriglyceridemic subjects are mainly due to increased plasma levels of coagulation factor XIII and PAI-1. It could also be demonstrated that plasma clotting factors VII and VIII activities as well as plasma fibrinogen and von Willebrand factor levels were higher in patients with type 2 diabetes and abdominal obesity than in diabetics without obesity. Such findings are supporting data in the literature, insisting on the pathogenic relevance of intraabdominal obesity and of the subsequently enhanced release of fatty acids and of proinflammatory cytokines in the portal flow. Surprisingly anticoagulant plasma proteins C and S levels were found to be increased in overweight and hyperlipidemic patients considered to be at risk for thrombotic complications. Recent data in the literature had however demonstrated that circulating protein C zymogen acquires anticoagulant activity only after its binding to specific receptors on endothelial cell membrane, while proinflammatory cytokines may disrupt this activating interaction with vascular endothelia.

11 citations

Journal ArticleDOI
TL;DR: The results show that circulating adiponectin is associated with reduced manifestations of ALP, including HDL subclasses, and was independent of apoB and TG levels (p<0.05), but not of apOAI and HOMA-IR.
Abstract: Background and aims This study examined the relationships between plasma levels of adiponectin and the features of the atherogenic lipoprotein phenotype (ALP), including HDL subclasses. Methods and results Blood lipids and apolipoproteins were measured in 293 healthy individuals. LDL particle size and HDL subspecies (HDL 2 , HDL 3 ) were measured using gradient gel electrophoresis. Plasma adiponectin levels were negatively correlated with levels of apoB ( r =−0.199, p r =−0.262, p r =−0.323, p r =0.173, p =0.006), HDL-cholesterol ( r =0.287, p r =0.289, p p p 2b ( r =0.204, p 2a ( r =0.132, p 3a ( r =−0.128, p 3b ( r =−0.203, p 3c ( r =−0.159, p 2 (HDL 2b +HDL 2a ) was independent of apoB and TG levels ( p Conclusions Our results show that circulating adiponectin is associated with reduced manifestations of ALP.

10 citations

Journal ArticleDOI
TL;DR: There was a significant and positive association between PK and fasting levels of total cholesterol, non-high-density lipoprotein cholesterol, and triglycerides, and it was found that children with a family history of CVD had significantly elevated PK activity.
Abstract: Plasma prekallikrein (PK) has been shown to be associated with cardiovascular disease (CVD) and its risk factors, but these associations have not been investigated in children. The present study ex...

10 citations