Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial dysfunction with atherosclerosis is a recognized complication of uremic patients. The hypoalbuminemia of peritoneal dialysis (PD) patients can induce a hypercoagulable and atherogenic state. In this study, we investigated the role played by malnutrition-inflammation syndrome on endothelial function markers in PD patients. We measured markers of nutrition [normalized protein catabolic rate (nPCR), albumin, prealbumin, insulin-like growth factor 1 (IGF-1), transferrin, and cholesterol], markers of endothelial damage and function [tissue-type plasminogen activator (tPA), thrombomodulin (TM), von Willebrand factor (vWF), and NO3 (representing NO)], markers of a coagulable state [fibrinogen and plasminogen activator inhibitor 1 (PAI-1)], markers of inflammation [tumor necrosis factor alpha (TNF alpha) and C-reactive protein (CRP)], and other endothelial injury factors [lipoprotein(a) [Lp(a)] and homocysteine]. We also performed an endothelial stimulation test consisting of right-arm venous occlusion (VO) for 10 minutes. The patients were divided into four groups according to their clinical atherosclerotic score (CAS). We studied 45 clinically stable PD patients. At baseline, statistically significant negative linear correlations were found between albumin and age (r = -0.54, p < 0.05), albumin and vWF post-VO (r = -0.54, p < 0.05), and albumin and TM (r = -0.36, p < 0.05), which are endothelial damage markers and prothrombotic factors. A positive linear correlation was seen between albumin and NO3 post-VO (r = 0.48, p < 0.05), indicating a high vasodilatation capacity. C-Reactive protein and TNF alpha showed a positive linear correlation (r = 0.5, p < 0.01). Similarly, TNF alpha showed a positive linear correlation with cardiovascular risk markers such as fibrinogen (r = 0.79, p < 0.01), PAI-1 (r = 0.44, p < 0.05), and homocysteine (r = 0.37, p < 0.05). Creatinine clearance showed a negative linear correlation with TM (r = -0.36, p < 0.05). Patients with albumin < 4 g/dL showed a lower tPA ratio, lower NO3, and a higher CRP, TNF alpha, and Lp(a) than did patients with albumin > 4 g/dL [tPA ratio: 2.1 +/- 1.56 (n = 29) vs. 2.6 +/- 2.3 (n = 16), p < 0.05; NO3: 47 +/- 27 micrograms/mL vs. 69 +/- 33 micrograms/mL, p < 0.05; CRP: 1.8 +/- 3 mg/dL vs. 1.1 +/- 1.6 mg/dL, p < 0.05; TNF alpha: 44.4 +/- 16 pg/mL vs. 36.6 +/- 21.4 pg/mL, p < 0.05; Lp(a): 55 +/- 39 mg/dL vs. 33 +/- 21 mg/dL, p < 0.05]. Patients with a worse CAS showed higher homocysteine levels and lower albumin values. Those relationships were maintained in both periods of the study. We found no relationships between dialysis dose and endothelial function markers. In conclusion, malnutrition-inflammation syndrome may contribute to endothelial dysfunction and, consequently, to prothrombotic and proatherogenic processes in PD patients.
 ...
PMID:Malnutrition-inflammation syndrome is associated with endothelial dysfunction in peritoneal dialysis patients. 1476 71

Moderate hyperhomocysteinemia is associated with an increased risk of atherosclerosis, thrombosis and neurodegenerative diseases. Homocysteine accumulation in the blood can be due to many underlying causes, which may interact with each other, e.g. genetic disposition and B-vitamin status. The role of the sulfur-containing amino acid homocysteine in the pathogenesis of diseases remains unclear, even if many studies suggest a causal relationship between homocysteine-mediated processes like oxidative stress, NO-inactivation and endothelial deficiency and atherogenesis. Proposed mechanisms of action of homocysteine are discussed, and the question is addressed, whether effects that are attributed to homocysteine, are not rather the consequence of folate and vitamin B12-deficiency. Deficiency of these B-vitamins in parallel with moderate hyperhomocysteinemia is often found in patients with enhanced activation of the cellular immune system, like Alzheimer's disease, rheumatoid arthritis and also vascular diseases. In patients with these diseases an association between homocysteine metabolism, oxidative stress and immune activation exists. On the one hand proliferation of immunocompetent cells having an enhanced demand for B-vitamins leads to the accumulation of homocysteine. On the other hand macrophages stimulated by TH1-type cytokine interferon-gamma form reactive oxygen species (ROS), which oxidize antioxidants, lipoproteins and oxidation-sensitive B-vitamins. Thereby Th1-type immune response could contribute importantly to the development of hyperhomocysteinemia, and may also be a major determinant of disease progression.
 ...
PMID:Moderate hyperhomocysteinemia and immune activation. 1496 13

Cardiovascular disease (CVD) is the major cause of death in end-stage renal disease (ESRD). Malnutrition may worsen patient outcome by aggravating existing inflammation and heart failure, accelerating atherosclerosis and increasing susceptibility to infection. Available data demonstrate that chronic inflammation, a non-traditional risk factor which is observed commonly in uremic patients, play a key role in the genesis of both malnutrition and CVD in ESRD. Moreover, inflammation is associated with congestive heart failure. Pro-inflammatory cytokines are pivotal to the inflammation. There is evidence that a chronic inflammation with activation of C-reactive protein, interleukin-6, tumour necrosis factor alpha and other cytokines is associated with increased oxidative stress and endothelial dysfunction in ESRD patients. Strong relations between malnutrition, inflammation and atherosclerosis in ESRD patients suggest the presence of a MIA (malnutrition, inflammation, and atherosclerosis) syndrome, which is associated with high mortality rate. Thus, it could be speculated that suppression of the vicious cycle of malnutrition, inflammation and atherosclerosis (MIA) would improve survival in ESRD patients. Therefore, the early stage of chronic renal failure is the ideal time to start therapeutic interventions.
 ...
PMID:[Malnutrition -- inflammation -- atherosclerosis (MIA syndrome) in patients with renal failure]. 1497 61

Cardiovascular disease is common in patients with chronic kidney disease (CKD). As renal function fails, many patients become progressively malnourished, as evidenced by reduced levels of albumin, prealbumin, and transferrin. Malnourished patients have increased levels of C reactive protein (CRP), interleukin-6 (IL-6), and concomitant cardiovascular disease when they reach end stage. Many diseases that cause CKD, diabetes, and hypertension are also associated with cardiovascular disease. Thus the direct effect of renal failure per se directly contributing to the inflammation-malnutrition-atherosclerosis paradigm is not completely established in early stages of CKD. Some aspects of progressive renal failure, however, cause changes in plasma composition and endothelial structure and function that favor vascular injury. As renal function fails, hepatic apo A-I synthesis decreases and HDL levels fall. HDL is an important antioxidant and defends the endothelium from the effects of cytokines. Inflammation causes further structural and functional abnormalities in HDL. Apolipoprotein C III (apo C III), a competitive inhibitor of lipoprotein lipase is increased in CKD. Serum triglyceride levels increase as a result of accumulation of intermediate-density lipoprotein (IDL) comprising VLDL and chylomicron remnants. These impede vascular relaxation and are associated with cardiovascular disease. Activation of the renin angiotensin axis is a component of many renal diseases and adaptation to loss of renal mass. Angiotensin II (AngII) activates NADPH oxidases, leading to production of the superoxide anion and decreased availability of nitric oxide (NO), further impairing vascular function. H(2)O(2), produced as a consequence of superoxide dismutation, stimulates vascular cell proliferation and hypertrophy. Leukocyte-derived myeloperoxidase functions as an "NO Oxidase" in the inflamed vasculature and contributes to decreased NO bioavailability and compromised vascular reactivity. The changes in lipoprotein composition and structure as well as AngII-mediated alterations in endothelial function amplify the effect of subsequent inflammatory events.
 ...
PMID:The role of oxidative stress-altered lipoprotein structure and function and microinflammation on cardiovascular risk in patients with minor renal dysfunction. 1497 55

Longitudinal associations of malnutrition with atherosclerotic events in uremia are unclear. In 50,732 incident Medicare dialysis patients who had normal (18.5 to 24.9 kg/m(2)), low (<18.5 kg/m(2)), or high (> or = 25 kg/m(2)) body mass index (BMI) and initiated dialysis in the United States from January 1995 to December 1999 with reported measured creatinine clearances and acute coronary syndrome (ACS; International Classification of Diseases, Ninth Revision codes 410.x and 411.x) were examined in parametric survival models. Normal BMI was the referent group. Twenty-four-hour urinary creatinine (UCr) was used as a measure of muscle mass. There were 7213 (14.2%) hospitalized ACS events, 1528 (22%) of which were fatal (death within 30 d). One-year post-ACS mortality was 48%. Low BMI (hazard ratio [HR], 0.89; P = 0.02] was associated with lower hazard, and UCr was not predictive (NS) of hospitalized ACS in multivariable model. Low BMI (NS) was not associated with a composite end point of hospitalized ACS/suspected out-of-hospital ACS death, whereas lowest UCr quartile was associated with higher hazard (HR, 1.14; P < 0.001). Low BMI (HR, 1.24; P < 0.001) and decrease in UCr (highest quartile reference, second quartile HR, 1.11 [P < 0.001]; third quartile HR, 1.24 [P < 0.001]; and fourth quartile HR, 1.43 [P < 0.001]) were associated with increased hazard of death. Hospitalized ACS events in dialysis patients carry very high immediate and long-term mortality. Positive longitudinal associations of malnutrition with documented hospitalized ACS events could not be demonstrated. Further longitudinal studies are warranted to provide definitive evidence of malnutrition as a uremic risk factor for atherosclerosis.
 ...
PMID:Malnutrition and atherosclerosis in dialysis patients. 1497 76

The association of high body mass index (BMI) with better survival in chronic kidney disease (CKD) is considered a "risk factor paradox" or "reverse epidemiology." Since malnutrition is a powerful predictor of death and cardiovascular disease is its leading cause, it has been suggested that malnutrition and atherosclerosis must be associated. Thus the current paradigm is that malnutrition is a risk factor for atherosclerosis and obesity is protective in CKD patients. We recently showed that high-BMI patients with inferred high body fat have an increased prevalence of atherosclerosis and subsequent cardiovascular and all-cause mortality. Prior cross-sectional studies also showed that high BMI in CKD is associated with higher C-reactive protein (CRP) levels and increased coronary calcification on electron beam computed tomography (CT) scan. These apparently conflicting data on better survival but increased inflammation and atherosclerosis in high-BMI CKD patients could be explained as follows. It is hypothesized that nutrition exerts a much stronger influence on survival than atherosclerosis in CKD. Malnutrition strongly augments the hazard of death from coexistent diseases, while better nutrition has the opposite effect. Thus the risk of death is highest in malnourished patients (low muscle and low fat mass) and lowest in well-nourished patients (high BMI, high muscle mass). Obesity (high BMI, high fat mass) is associated with inflammation and atherosclerosis. The risk of death from obesity and atherosclerosis is increased, but not so much as occurs with malnutrition. Therefore high body fat patients have intermediate survival. Thus it is postulated that an association of obesity, inflammation, and atherosclerosis (OIA syndrome) might exist in CKD.
 ...
PMID:The body mass index paradox and an obesity, inflammation, and atherosclerosis syndrome in chronic kidney disease. 1514 50

The role of glutathione (GSH) in inflammation is largely discussed from the context of providing reducing equivalents to detoxify reactive oxygen and nitrogen species. Inflammation is now recognized to be an underlying cause of many vascular diseases including atherosclerosis, a disease in which endothelial GSH concentrations are decreased. However, mechanisms that control GSH levels are poorly understood. Key players in the inflammatory process are endothelial adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1). This adhesion molecule is present constitutively and can be induced by a variety of inflammatory stimuli. In this study, using mouse aortic endothelial cells (MAEC) deficient in ICAM-1, we demonstrate a novel interplay between constitutive ICAM-1 and cellular GSH. Deficiency of ICAM-1 was associated with an approximately twofold increase in total GSH content. Inhibiting glutamate-cysteine ligase (GCL), the enzyme that catalyses the rate-limiting step in GSH biosynthesis, prevented the increase in GSH. In addition, the catalytic subunit of GCL was increased (approximately 1.6-fold) in ICAM-1 deficient relative to wild-type cells, suggesting that constitutive ICAM-1 represses GCL expression. Furthermore, the ratio of reduced (GSH) to oxidized (GSSG) glutathione was also increased suggesting a role for ICAM-1 in modulating cellular redox status. Interestingly, increasing cytosolic GSH in wild-type mouse endothelial cells decreased constitutive ICAM-1, suggesting the presence of an inverse and reciprocal pathway. To test the effects of inducible ICAM-1 on GSH, cells were stimulated with the proinflammatory cytokine TNF-alpha. TNF-alpha stimulated production of ICAM-1, which was however not associated with induction of GSH. In contrast, supplementation of endothelial cells with GSH before TNF-alpha addition, inhibited induction of ICAM-1. These data suggest a novel regulatory pathway between constitutive ICAM-1 and GSH synthesis in the endothelium and are discussed in the context of modulating the inflammatory response.
 ...
PMID:Regulation of endothelial glutathione by ICAM-1: implications for inflammation. 1518 Sep 61

Cardiovascular disease (CVD) is the major cause of death in end-stage renal disease (ESRD) patients. Uremic malnutrition and chronic inflammation are important comorbid conditions, closely associated with CVD risk in ESRD patients. A pathophysiologic link between uremic malnutrition, chronic inflammation, and atherosclerosis has been proposed in this patient population. Uremic malnutrition can result from chronic inflammation and can accelerate the progression of cardiovascular disease. Chronic inflammation can also directly predispose ESRD patients to a proatherogenic state. Both uremic malnutrition and chronic inflammation are also associated with increased oxidative stress, a condition proposed as a unifying concept of CVD in uremia. Although a single common etiology has not been identified in this complex process, nutritional, anti-inflammatory, and antioxidant interventions can provide potential treatment options to improve the high mortality and morbidity in ESRD patients.
 ...
PMID:Role of nutrition for cardiovascular risk reduction in chronic kidney disease patients. 1521 87

Malnutrition, anemia and increased atherosclerosis are the main causes of mortality in hemodialysis patients. Therapies designed to improve the disorders might therefore be expected to improve outcome. The effects of Nandrolone Decanoate (ND), in 64 stable hemodialysis patients, were studied with respect to the following parameters: nutritional status, hematological indexes, lipid profiles including serum levels of lipoprotein(a) [Lp(a)] in terms of differences in apolipoprotein(a) [apo(a)]. The patients were treated with ND at dose of 100 mg/I.M./week for 4 months. After 2 and 4 months of treatment the elevations in the serum levels of albumin (p < 0.0001), creatinine (p < 0.009), hemoglobin (p < 0.03), hematocrit (p < 0.03), cholesterol (p = 0.007) and triglyceride (p < 0.04) were noticed. Marked decrease in the concentration of high-density lipoprotein cholesterol (p = 0.007) and Lp(a) (p < 0.0001) were also found. These effects after 2 months of treatment withdrawal were relatively constant. By dividing patients according to the baseline Lp(a) levels and molecular weight of apo(a) isoform, it was noticed that the decrease in serum Lp(a) was significant in patients with high Lp(a) (> 30 mg/dl) than those of with low Lp(a) (< 30 mg/dl), irrespective of apo(a) molecular weight. It may be suggested that, ND has beneficial effect on nutritional status and treatment of anemia in hemodialysis patients. In spite the adverse effect of ND on lipid profile, it decreases Lp(a) mostly in patients with high serum Lp(a) preferently by the effect on apo(a) gene transcriptional activity.
 ...
PMID:Effect of Nandrolone Decanoate on serum lipoprotein (a) and its isoforms in hemodialysis patients. 1522 79

The uraemic syndrome is a complex condition that results from the retention of "waste" compounds that normally would be excreted into the urine or catabolized by the kidneys. In addition, inflammation has been implicated in symptoms associated with uraemia, including its role in the malnutrition-inflammation-atherosclerosis syndrome. Regarding vascular disease, traditional risk factors such as hypertension and gender do not seem to have the same significance in the uraemic population compared with patients without renal failure, and so the possibility has been raised that the uraemic toxins that result in the uraemic syndrome could play a role in this process. In this review, various questions are addressed regarding the involvement of cytokines in uraemia and the effects of dialysis membranes and fluids in patients receiving haemodialysis or peritoneal dialysis on cytokine levels. The effects of non-dialysis-related factors on levels of cytokines, mortality rates and other uraemic disorders are also discussed. It is concluded that cytokines are undoubtedly retained in uraemia, and that the loss of renal excretion almost certainly plays a key role in this process. Many cytokines have a pro-inflammatory role, probably resulting in a number of clinical events that are related to the increased morbidity and mortality of uraemic and haemodialysis patients. Any adjustment of the subtle balance between pro- and anti-inflammation by medical interventions should be conducted carefully because of an enhanced risk of serious infectious episodes. Bioincompatibility of dialysis techniques probably enhances the generation of cytokines as well as other uraemic toxins.
 ...
PMID:Interleukin/cytokine profiles in haemodialysis and in continuous peritoneal dialysis. 1528 59


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>