Relationship among plasma secretory phospholipase A2, oxidized low density lipoprotein & paraoxonase activities in hypertensive subjects treated with angiotensin converting enzyme inhibitors.

BACKGROUND & OBJECTIVE: Secretory phospholipase A(2) (sPLA(2)) and oxidized low density lipoprotein (oxLDL) are considered as oxidative and inflammatory markers. The effects of oxLDL have been shown to be inhibited by paraoxonase (PON1). This study was undertaken to investigate the relationship between oxidative and inflammatory markers in hypertensive patients with or without antihypertensive drug treatment. METHODS: Newly diagnosed hypertensive patients (n=35) and hypertensive patients who had been taking angiotensin converting enzyme (ACE) inhibitors as antihypertensive therapy (10 or 20 mg/day for 9 +/- 2 wk; n=35) and age-matched normotensive subjects (controls; n=20) were included in this study. Plasma sPLA(2), oxLDL and PON1 activities were determined. RESULTS: Hypertensives had higher plasma oxLDL and sPLA(2) levels (P<0.01) and lower PON1 levels than the controls (P<0.01). Treated hypertensives had lower plasma sPLA< and oxLDL levels and higher PON1 activities than hypertensives (P<0.01). sPLA(2) was positively correlated with oxLDL (r=0.433, P<0.01) and negatively correlated with plasma PON1 (r=-0.540, P<0.01) in untreated hypertensives. In controls and treated hypertensives, plasma PON1 was positively correlated with oxLDL (r=0.455, r=0.429, P<0.01, respectively) and sPLA(2) (r=0.450, r=0.506, P<0.01, respectively). INTERPRETATION & CONCLUSION: Reduction in PON1 activity and elevation in both sPLA(2) activities and oxLDL levels might be involved in elevated oxidative stress and inflammation. ACE inhibitor treatment may help reduce inflammation and oxidative stress in hypertensives.

The relationship between plasma asymmetrical dimethyl-L-arginine and inflammation and adhesion molecule levels in subjects with normal, impaired, and diabetic glucose tolerance.

Increasing evidence suggests that the postprandial state is a contributing factor to the development of atherosclerosis. To evaluate the effects of acute hyperglycemia on endothelial dysfunction and inflammation, plasma asymmetrical dimethyl-l-arginine (ADMA), intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1, and C-reactive protein (CRP) levels and secretory phospholipase A(2) (sPLA(2)) activities were measured in subjects with normal (n = 35), impaired (IGT) (n = 25), and diabetic (DGT) (n = 20) glucose tolerance. At baseline, plasma ADMA, sICAM-1, and CRP concentrations and plasma sPLA(2) activities were higher in both the IGT and DGT groups than in the normal glucose tolerance group (for each comparison, each P < .001). Patients with DGT have higher plasma ADMA and sICAM-1 concentrations than patients with IGT (for each, P < .001).Two hours after glucose loading, plasma ADMA and CRP concentrations and sPLA(2) activities were significantly elevated in the 3 groups when compared with baseline levels (for each comparison, P < .001). Plasma vascular cell adhesion molecule 1 and sICAM-1 concentrations were found to be elevated from baseline levels after glucose loading in the IGT and DGT groups (for each comparison, P < .001). Correlation analysis at baseline suggested that there was a significant relationship between ADMA and inflammation and soluble adhesion markers in the studied groups. In conclusion, plasma concentrations of ADMA and of inflammation and adhesion molecules were elevated in the prediabetic state. A complex interrelation could exist between ADMA and inflammation, and mechanisms involved in endothelial dysfunction are multifactorial at the prediabetic and diabetic state.

Plasma leptin and its relationship with lipid peroxidation and nitric oxide in obese female patients with or without hypertension.

BACKGROUND: Recent evidence suggested that leptin-induced oxidative stress in human endothelial cells in vivo and increased oxidative stress in human essential hypertension may further contribute to both the development of atherosclerosis and other cardiovascular diseases. We investigated the association of plasma leptin levels with plasma lipid peroxidation and nitric oxide metabolites (NOx) in obese hypertensive atherosclerosis model. METHODS: Plasma leptin, lipid peroxidation and NOx levels were determined in age-matched non-obese normotensive female subjects (n = 30), obese normotensive female subjects (n = 45), and obese hypertensive female subjects (n = 50). Plasma leptin levels were determined by immunoradiometric method. Lipid peroxidation was determined as thiobarbituric acid reactive substances (TBARS) using spectrophotometric method. NOx levels were determined using enzymatic method. RESULTS: We found that plasma leptin and TBARS levels were increased in obesity, and obese hypertensives have significantly higher plasma leptin and TBARS levels than obese normotensives (p <0.001 and p <0.001). Obese hypertensives have significantly lower plasma NOx levels than obese normotensives (p <0.001). In univariate and multivariate regression analysis, plasma leptin levels were significantly correlated with TBARS (p <0.01 and p <0.01) in obese subjects. Plasma TBARS were also inversely correlated with NOx in hypertensive obese subjects (r = -0.412, p <0.01). CONCLUSIONS: Our results have shown that elevated leptin levels may be associated with increased oxidative stress and free-radical-induced decreased NOx levels. Therefore, hyperleptinemia may be an important contributor to the generation of hypertension in obesity.

Plasma total homocysteine concentrations in obese and non-obese female patients with type 2 diabetes mellitus; its relations with plasma oxidative stress and nitric oxide levels.

Hyperhomocysteinemia has been identified as independent risk factor for early atherosclerotic vascular disease. The purpose of our study was to investigate the plasma homocystein (Hcy) concentrations and its relationship with lipid peroxidation as thiobarbituric acid reactive substances (TBARS) and nitric oxide (NOx; nitrite plus nitrate) concentrations in age-matched non-obese (n=55) and obese (n=60) female subjects with type 2 diabetes mellitus. Non-obese diabetic patients have significantly higher plasma tHcy and TBARS (p<0.001 and p<0.001), and significantly lower NOx concentrations than the controls (n=25) (p<0.001). The plasma tHcy and TBARS concentrations were higher and nitric oxide concentrations were lower in obese diabetics than in non-obese diabetics (for each comparison; p<0.001). Correlation analysis demonstrated that there was a significant positive correlation between tHcy and TBARS (r=0.452, p<0.01) in diabetics groups. There was no significant correlation between tHcy and plasma NOx, insulin and blood pressure. We thought that Hcy might have a permissive role on the endothelium damage through free radical generating systems and the presence of obesity the free radical induced-damage has been elevated in diabetic patients.

Plasma homocysteine levels in obese and non-obese subjects with or without hypertension; its relationship with oxidative stress and copper.

OBJECTIVES: The relationship between plasma total Homocysteine (tHcy) and oxidative stress and plasma levels of lipids, insulin and copper levels were investigated in obese and nonobese hypertensives. DESIGN AND METHODS: Plasma tHcy levels were determined by an enzyme immunoassay method. Plasma lipid peroxidation levels were measured as thiobarbituric acid reactive substances (TBARS) by spectrophotometric methods. Plasma levels of copper and insulin were measured by atomic absorption spectrophotometer and electrochemiluminescence method, respectively. RESULTS: Plasma tHcy, copper and insulin levels did not differ in nonobese hypertensives compared to nonobese normotensives. Plasma TBARS levels were significantly increased in nonobese hypertensives when compared to nonobese normotensives (p < 0.001). Plasma tHcy, TBARS, copper and fasting insulin levels were significantly higher in obese normotensives and hypertensives than in nonobese normotensives and hypertensives, respectively (for each comparison; p < 0.001). There was a significant difference in plasma tHcy, TBARS and copper levels between obese subjects with or without hypertension (for each comparison p < 0.01). The univariate analyses demonstrated a significant positive correlation between tHcy and TBARS (coefficient +/- SE, 0.411 +/- 0.115, p < 0.01) and copper (coefficient +/- SE, 0.425 +/- 0.135, p < 0.01) in obese subjects. In a multivariate regression analysis in obese subjects tHcy was positively correlated with TBARS (coefficient +/- SE, 0.480 +/- 0.155, p < 0.01) and copper (coefficient +/- SE, 0.486 +/- 0.140, p < 0.01). CONCLUSIONS: We hypothesize that in the presence of other traditional risk factors, Hcy may have a permissive role in the endothelium damage even within the normal range and this role may be related to free radical generating systems. Therefore, modest elevation of plasma Hcy may causally be involved in the pathogenesis of atherosclerosis and/or cardiovascular disease.

Relationship between plasma leptin and zinc levels and the effect of insulin and oxidative stress on leptin levels in obese diabetic patients.

Leptin is thought to be a lipostatic signal that contributes to body weight regulation. Zinc plays an important role in appetite regulation also. Our aim is to evaluate the relationship between leptin and zinc in obese and nonobese type 2 diabetic patients and its relationship with oxidative stress and insulin. We studied 25 nonobese nondiabetic women (controls); 35 nonobese diabetic women; and 45 obese diabetic women. Plasma leptin concentration was determined by immunoradiometric assay. Thiobarbituric acid reactive substances (TBARS), markers of oxidative stress, were assayed by the spectrofotometric method. Plasma levels of zinc and insulin were measured by atomic absorption spectrophotometer and electrochemiluminescence methods, respectively. We found that nonobese diabetic patients had significantly lower zinc and higher TBARS levels than control subjects (P<0.01). There was no difference in plasma leptin levels between nonobese diabetic subjects and controls. Obese diabetic subjects had significantly higher plasma leptin, TBARS, and insulin levels and significantly lower plasma zinc levels than nonobese diabetic subjects (for each comparison; P<0.01). The univariate and multivariate analyses demonstrated a significant positive correlation between leptin and body mass index (P<0.01) and insulin (P<0.01), and a significant negative correlation between leptin and zinc in obese subjects. Additionally, TBARS levels was positive correlated with insulin and negative correlated with zinc in obese diabetic subjects. We conclude that zinc may be a mediator of the effects of leptin, although the detailed mechanism is still unknown and requires further investigation. Free radical induced mechanism(s) may be involved in this process.

Interleukin-33, matrix metalloproteinase-9, and tissue inhibitor [corrected] of matrix metalloproteinase-1 in myocardial infarction.

BACKGROUND/AIMS: Acute coronary syndrome (ACS) is characterized by increased inflammatory processes and endothelial activation. We investigated the association between ACS and inflammatory mediators and matrix-degrading enzymes. METHODS: We prospectively enrolled 55 consecutive patients with ACS: 25 with unstable angina (UA) and 30 with non-ST elevated myocardial infarction (NSTEMI). For comparison, 25 age- and sex-matched subjects with no significant coronary artery stenosis were included as the control group. Peripheral serum levels of interleukin (IL)-33, matrix metalloproteinase (MMP)-9, tissue inhibitor of MMP-1, and C-reactive protein (CRP) were measured on admission, and at 12, 24, 48, and 72 hours after the initial evaluation. RESULTS: Compared to serum levels in the control group, serum levels of IL-33 decreased in the NSTEMI group (p < 0.05), and levels of MMP-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 increased in the UA group (p < 0.01, p < 0.05, respectively) and NSTEMI group (p < 0.05, p < 0.05, respectively). IL-33 levels were significantly lower on admission than at 12 hours after the initial evaluation (p < 0.05). IL-33 levels were negatively correlated with MMP-9 levels (r = -0.461, p < 0.05) and CRP levels (r = -0.441, p < 0.05). CONCLUSIONS: Elevated levels of MMP-9, TIMP-1, and decreased levels of IL-33 play a role in the development and progression of ACS.