The effects of hypothyroidism on the mechanical properties and histomorphological structure of the thoracic aorta.

This experimental study investigates the effects of hypothyroidism on the descending thoracic aorta. Hypothyroidism was induced in 20 male Wistar rats by administering 0.05% of 6-n propyl 2-thiouracil (PTU) in their drinking water for 8 weeks. Euthyroid rats were used as controls. Animals were sacrificed and longitudinal strips of the descending aorta were subjected to various preselected levels of stress in a uniaxial tensile-testing device. Analysis of stress-strain, elastic modulus-strain curves disclosed significant differences between groups, indicative of stiffer aortas in hypothyroid animals at the upper physiologic and higher levels of pressure. Remodeling of the aortic wall of hypothyroid animals revealed significant histological changes. The thoracic aorta of hypothyroid rats compared with that of euthyroid ones became stiffer at high strains, including the upper physiologic range, loosing part of its distensibility. Hypothyroidism was also associated with diameter enlargement and substantial lengthening of the aorta.

Regulatory effect of parathyroid hormone on sRANKL-osteoprotegerin in hemodialysis patients with renal bone disease.

Receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin are newly identified molecules that contribute to the modulation of bone remodeling. RANKL activates osteoclast function by binding to RANK in either a soluble or membrane-bound form, whereas osteoprotegerin (OPG) neutralizes its effects. The aim of this study is the evaluation of soluble RANKL (sRANKL)-OPG in cohorts of hemodialysis patients and the establishment of possible correlations between their serum levels and those of other biochemical markers. We measured intact parathyroid hormone (iPTH), osteocalcin (OC), OPG, alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) and sRANKL in 104 hemodialysis patients. The patients were studied as a whole and in two subgroups according to their bone turnover state. In patients with low serum levels of bone turnover markers (intact parathyroid hormone [iPTH] < 100 pg/mL, ALP < 100 U/L, TRAP < 4 U/L; 33 patients), the following correlations were found: (i) positive correlations of iPTH with RANKL (r = 0.394, P = 0.023) and RANKL/OPG ratio (r = 0.49, P = 0.004); (ii) a negative correlation between iPTH and OPG (r = -0.365, P = 0.037). The subgroup of patients with normal or high serum levels of bone turnover markers (iPTH >or= 150 pg/mL, ALP >or= 100 U/L, OC >or= 40 ng/mL; 19 patients) exhibited the following significant correlations: (i) a positive correlation between OPG and iPTH serum level (r = 0.649, P = 0.003); and (ii) a negative correlation between RANKL/OPG ratio and iPTH (r = -0.464, P = 0.045). In conclusion, the observation that PTH favors RANKL and inhibits OPG production was only demonstrated in the serum of hemodialysis patients in a low turnover state. The positive correlation between serum OPG and iPTH in normal or high turnover rates implies a homeostatic mechanism to limit bone resorption, probably associated with skeletal resistance to PTH.

Hypothyroidism and the aorta. evidence of increased oxidative DNA damage to the aorta of hypothyroid rats.

BACKGROUND: Although it has been suggested that the hypometabolic state is associated with a decrease in oxidative stress, literature data are controversial, revealing an individuality of oxidant status in relation to tissue properties and responsiveness. Hypothyroidism has profound direct and indirect actions on the vascular system, inducing characteristic hemodynamic changes while the aorta represents an important determinant of vascular performance. This study aims to examine the oxidant status on the aorta in chronic experimental hypothyroidism. MATERIALS AND METHODS: Chronic hypothyroidism was successfully induced in 20 male Wistar rats by administration of 0.05% 6-n-propyl 2-thiouracil in their drinking water for 8 weeks. Age-matched euthyroid rats were used as controls. Lipid peroxidation in the serum was determined by the end-product malondialdehyde (MDA). Oxidative damage to genomic DNA of aortic tissue and serum was investigated by measuring 8-oxo-dG, one of the base modifications produced in DNA by the reaction of reactive oxygen species. Serum lipids measurement was performed. RESULTS: A hypothyroid state was confirmed by levels of serum thyroid hormones, lipidemic profile, clinical examination, pathological findings and cardiovascular hemodynamics parameters. Hypothyroidism was associated with a significant increase in lipid peroxidation. (MDA 1.44 +/-0.93 vs 0.64 +/- 0.53 nmol/l, p < 0 .01). Levels of 8-oxo-dG on the aortic ring, expressing the oxidant damage on genomic DNA and in the serum, were observed to be significantly raised in the hypothyroid group compared to controls (8-oxodG(serum) 29.22 +/- 17.78 vs. 17.56 +/- 4.44 ng/ml, p < 0.01; 8-oxo-dG(aorta)11.58 +/- 2.70 vs. 4.09 +/- 1.27 ng/ml, p < 0. 001). A statistical correlation between measurements of 8-oxo-dG in the aorta and serum was found (correlation coefficient = 0.36, p < 0.05). A hyperlipidemic profile in hypothyroid animals was revealed. CONCLUSION: Vascular oxidative stress seems to play a pivotal role in the evolution of vascular pathology. Hypothyroidism was associated with increased DNA oxidative damage to the aorta. Hypercholesterolemia and an increase in mean arterial pressure associated with hypothyroidism may have a contributive role in the accumulation of damage in nuclear DNA of the vascular wall. 8-Oxo-dG is one of the mutagenic base modifications produced in DNA. Although clinical studies in other tissues have indicated a direct correlation between in vivo 8-oxo-dG formation and pathological processes, its role on the vascular wall needs further investigation.

Association between plasma levels and immunolocalization of cytokines in heart valve lesions: a possible target for treatment?

OBJECTIVE: To compare the distribution of pro-inflammatory cytokines in heart valve lesions with their plasma levels. METHODS: Plasma levels of TNF-alpha and IL-10 were determined in 70 patients with heart valve lesions. TNF-alpha and IL-6 levels were also quantified in tissue specimens obtained from these patients after valve replacement. RESULTS: Plasma concentrations of TNF-alpha and the extent of calcium deposits were significantly higher in patients with aortic valve stenosis compared with individuals with mitral valve stenosis. A direct relationship was demonstrated between TNF-alpha blood and tissue levels. There was an increase in TNF-alpha and IL-6 tissue immunoreactivity with the progression of heart valve disease from mild to advanced inflammation. The increased accumulation of calcium deposits in damaged heart valves correlated with plasma TNF-alpha and IL-10 levels. CONCLUSIONS: The association between plasma and tissue sample cytokine concentrations suggests that plasma cytokine levels reflect the extent and severity of valvular lesions. Statins may attenuate progressive calcific valve stenosis. Statins also affect TNF-alpha and IL-10 plasma levels. These associations may help not only predict the progression but also attenuate the deterioration of valvular lesions. Verification of these results in larger scale studies is required before definite conclusions can be drawn.

Apolipoprotein J and leptin levels in patients with coronary heart disease.

BACKGROUND: Preliminary data suggest that apolipoprotein J (ApoJ) may play a role in the development and progression of atherosclerosis. Leptin, an adipose tissue hormone, exerts important cardiovascular effects. The association between serum ApoJ and leptin concentrations was assessed in patients with established or suspected coronary heart disease (CHD). PATIENTS AND METHODS: Serum ApoJ and leptin concentrations were evaluated in 67 CHD patients undergoing coronary angiography [54 individuals with significant (> or =50%) coronary artery stenosis and 13 patients without significant coronary artery stenosis on angiography]. RESULTS: Serum ApoJ concentrations in patients with significant coronary artery stenosis were significantly higher than in those without (303.9+/-118.6 vs. 121.2+/-37.5 microg/mL, respectively; p<0.001). The reverse pattern was observed for serum leptin levels (8.6+/-5.5 vs. 20.6+/-17.1 ng/ml, respectively; p=0.016). There was a significant negative correlation between ApoJ and leptin levels (r=-0.353; p=0.003). CONCLUSION: ApoJ and leptin may be markers for CHD.

Time-dependent alterations in serum NO concentration after oral administration of L-arginine, L-NAME, and allopurinol in intestinal ischemia/reperfusion.

OBJECTIVE: To study the effect of oral administration of a nitric oxide (NO) donor L-arginine (L-Arg), a NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and an inhibitor of xanthine oxidase, allopurinol (Allo), on serum NO concentration and catalase activity after intestinal ischemia/reperfusion (I/R) in rats. METHODS: Male Wistar rats receivedper os L-Arg (800 mg/kg) or L-NAME (50 mg/kg) or Allo (100 mg/kg) 24 hrs, 12 hrs and 1 hr before underwent 1 hr occlusion of superior mesenteric artery followed by 1 hr of reperfusion (L-Arg(IR1), L-NAME(IR1) and Allo(IR1) respectively) or 1 hr occlusion followed by 8 hrs of reperfusion (L-Arg(IR8), L-NAME(IR8) and Allo(IR8) respectively). There was one group underwent 1 hr occlusion (I), a group underwent 1 hr occlusion followed by 1 hr reperfusion (IR1), a group subjected to 1 hr occlusion followed by 8 hrs of reperfusion (IR8) and a last group that served as control (C). Serum NO concentration and catalase activity were measured. RESULTS: After 1 hr of reperfusion serum NO concentration was elevated in IR1 and L-Arg(IR1) groups compared with group C but not in L-NAME(IR1) and Allo(IR1) group. Catalase activity was enhanced in L-NAME(IR1) group. Interestingly, serum NO concentration was increased after 8 hrs of reperfusion in all groups (IR8, L-Arg(IR8), L-NAME(IR8) and Allo(IR8)) compared with control while catalase activity did not show significant difference in any group. CONCLUSIONS: The results of the present study show that NO concentration is elevated in serum after intestinal I/R and the elevation sustained after administration of L-Arg but not after administration of L-NAME or Allo after 1 hr reperfusion. However, after 8 hrs of reperfusion NO concentration was increased in all groups studied, focusing attention on its possible important role in a complicated situation such as intestinal I/R that involves intestine and other organs. Serum catalase activity does not seem to be affected by per os supplementation of L-Arg or Allo in intestinal I/R.

Effect of statins on serum apolipoprotein j and paraoxonase-1 levels in patients with ischemic heart disease undergoing coronary angiography.

It has been proposed that apolipoprotein J (apo J) and paraoxonase-1 (PON1) correlate with the extent and severity of ischemic heart disease (IHD). This article compares apo J and PON1 serum concentrations, PON1 activity, and the apo J/PON1 ratio in 138 IHD patients (64 statins users and 74 statin nonusers) referred for angiography and possible percutaneous coronary intervention. The effect of statin treatment on apo J and PON1 concentrations, PON1 activity, and the degree of coronary artery stenosis were evaluated. In both groups, apo J levels were increased, whereas PON1 concentration and activity decreased. IHD patients on statins had significantly lower apo J concentration and higher PON1 concentration and activity. Patients on statins had less coronary artery stenosis. High apo J levels, low PON1 levels, low PON1 activity, and a high apo J/PON1 ratio were associated with IHD. Statin treatment reverses these changes, probably by multiple beneficial actions.

The effect of sexual hormone abnormalities on proximal femur bone mineral density in hemodialysis patients and the possible role of RANKL.

Sexual hormone concentrations are commonly affected in chronic renal failure. The contribution of sex steroids to bone turnover regulation implies that sex steroid's dysfunction may be implicated in the emergence of renal osteodystrophy. This study was conducted to evaluate sex steroids and gonadotrophins in hemodialysis (HD) patients and to investigate their role in bone homeostasis in concert with other hormones and cytokines. Bone mineral density (BMD) at the proximal femur and intact parathyroid hormone (iPTH), osteoprotegerin, soluble receptor activator of NF-kappaB ligand (sRANKL), prolactin, total testosterone, estradiol, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured in serum samples in 42 patients, 21 men and 21 women, on maintenance HD therapy. Possible associations between clinical characteristics, biochemical parameters, and BMD values were investigated. In male HD patients, the testosterone concentration declined significantly with aging, whereas the estradiol level increased with longer duration of HD. Concurrently, testosterone correlated negatively with sRANKL concentrations (r=-0.520, p=0.016). Luteinizing hormone levels in male patients demonstrated statistically significant negative correlations with BMD values of the proximal femur. In the entire cohort of patients, FSH and LH were negatively associated with absolute values of proximal femur BMD. Gonadotrophin and sexual hormone concentrations in HD patients are associated with bone mineral status and consequently their derangements appear to contribute to the development of bone composition abnormalities in different types of renal osteodystrophy. Furthermore, testosterone's association with sRANKL levels in male HD patients suggests that RANKL may mediate the effect of testosterone on bone metabolism in these patients.

Correlation between lipid abnormalities and immunosuppressive therapy in renal transplant recipients with stable renal function.

BACKGROUND: Hyperlipidemia following successful renal transplantation is a frequent and persistent complication. Several immunosuppressive agents including cyclosporine A (CyA), corticosteroids, and tacrolimus appear to have a significant pathogenetic role. The aim of this study is to investigate the differential effects of different immunosuppressive agents on lipids in renal transplant patients. METHODS: Two groups of renal transplant recipients, each treated with a different combination of immunosuppressive agents, were studied: Group A (n = 13), cyclosporine A, mycophenolate mofetil (MMF), steroids, and basiliximab; Group B (n = 13), tacrolimus, MMF, steroids, and daclizumab). Plasma lipids [cholesterol (CHOL), low-density lipoprotein (LDL)-CHOL, high-density lipoprotein (HDL)-CHOL, and triglycerides (TG)] were examined before transplantation and 1 and 6 months posttransplantation. RESULTS: The patients treated with cyclosporine A-MMF showed a significant increase in mean cholesterol and mean LDL-cholesterol values at the 1-month posttransplantation follow-up compared with pretransplant levels (CHOL: 208.9 +/- 47.4 vs. 268.7 +/- 42.2 mg/dl, P = 0.004; LDL: 118.4 +/- 49.9 vs. 198.7 +/- 40.7 mg/dl, P = 0.002; pretransplant vs. 1 month, respectively). At 6 months, LDL-cholesterol levels were significantly elevated compared with pretransplant levels (LDL: 118.4 +/- 49.9 vs. 148.3 +/- 48.5 mg/dl, P = 0.034), whereas there was no significant change in the cholesterol level during the same period. In cyclosporine A-MMF-treated patients, plasma triglyceride levels were reduced at the 1- and 6-month follow-up (TG: 293.9 +/- 59.2 vs. 182.9 +/- 48.7 mg/dl, P = 0.03; 293.9 +/- 59.2 vs. 178.6 +/- 74.2 mg/dl, +/- = 0.023; pretransplant vs. 1 and 6 months, respectively). Patients receiving combined therapy with tacrolimus-MMF showed no significant changes in LDL-CHOL levels during the trial. Cholesterol levels at 6 months posttransplantation were significantly lower than the pretransplant measurements (CHOL: 182.9 +/- 44.4 vs. 162.3 +/- 37.2 mg/dl, P = 0.024; pretransplant vs. 6 months). A significant reduction in triglyceride level was documented at the 1-month follow-up followed by a subsequent decrease within 6 months (TG: 228.5 +/- 61.6 vs. 147.6 +/- 51.5 mg/dl, P = 0.005; TG: 228.5 +/- 61.6 vs. 130.4 +/- 54.7 mg/dl, P = 0.011; pretransplant vs. 1 and 6 months, respectively). CONCLUSIONS: In posttransplant patients with stable renal function cyclosporine therapy is associated with increased cholesterol and LDL-cholesterol levels. Hyperlipidemia is less pronounced in patients given tacrolimus. Tacrolimus appears to an immunosuppressant agent with fewer and less severe adverse effects on lipid metabolism.

The mechanical performance and histomorphological structure of the descending aorta in hyperthyroidism.

Thyroid hormones decrease systemic vascular resistance by directly affecting vascular smooth muscle relaxation. There is limited literature about their effect on the mechanical performance of the aortic wall. Therefore, the authors determined the influence of hyperthyroidism on the mechanical properties and histomorphological structure of the descending thoracic aorta in rats. Severe hyperthyroidism was induced in 20 male Wistar rats by administering L-thyroxine (T(4)) in their drinking water for 8 weeks; age-matched normal euthyroid rats acted as controls. Animals were sacrificed, and the mechanical and histomorphometrical characteristics of the descending thoracic aorta were studied. The aortic wall of hyperthyroid rats was stiffer than that of euthyroid animals at the upper physiologic levels of stress or strain (p < 0.05) but less stiff at the lower physiologic and lower levels (p < 0.05). The aorta of hyperthyroid animals compared with that of euthyroid ones showed an increase of the internal and external diameters (p < 0.05), the media area (p < 0.05), the number of smooth muscle cell nuclei (p < 0.05), and the collagen density (p < 0.05) and a decrease in the elastin laminae thickness (p < 0.001) and elastin density (p < 0.001). In hyperthyroid rats, the aortic wall was stiffer at the upper physiologic and higher levels of stress and strain. These changes correlated with microstructural changes of the aortic wall. The coexistence of hyperthyroidism with disease states or clinical conditions that predispose to increased arterial pressure may be associated with increased arterial stiffness and have undesirable consequences on the mechanical performance of the thoracic aorta and hemodynamic homeostasis. These changes could lead to an increased risk for developing vascular complications.

Hyperthyroidism is associated with increased aortic oxidative DNA damage in a rat model.

BACKGROUND: Hyperthyroidism is associated with increased oxidative stress and oxygen free radical production. Oxygen free radicals are implicated in several signalling pathways leading to vascular pathology. The present study evaluates the extent of aortic oxidative stress in experimental hyperthyroidism. MATERIALS AND METHODS: Chronic hyperthyroidism was induced in 20 male Wistar rats; another 20 animals served as controls. Oxidative damage to lipids and genomic DNA was assessed by measuring serum and aortic wall 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) levels (a mutagenic marker of oxidative DNA damage), as well as serum ceruloplasmin, malondialdehyde (MDA) and lipids. RESULTS: Hyperthyroid animals had significantly higher values of serum ceruloplasmin (11.27+/-1.16 vs. 9.58+/-1.17 mg/dl), MDA (5.34+/-1.32 vs. 0.64+/-0.53 nmol/ml) and 8-oxo-dG (33.91+/-9.63 vs. 17.56+/-4.44 ng/ml) compared with controls (p<0.001 for all associations). Aortic 8-oxo-dG levels were elevated in the thyrotoxic compared with the control group (13.01+/-2.38 vs. 4.09+/-1.27 ng/ml, respectively; p<0.001). 8-Oxo-dG measurements in aortic rings and in serum were positively correlated in the hyperthyroid rats (Pearson's correlation coefficient =0.66; p=0.007). CONCLUSION: Hyperthyroidism is associated with increased oxidative stress in the aortic wall. The animal model we describe has provided some preliminary data regarding the effect of hyperthyroidism on the vascular system. Verification of our results and further exploration of our animal model may help determine the association between oxidative DNA damage with functional changes of the vascular wall, such as endothelial function and vascular nitric oxide signalling.

Human soluble leptin receptor concentration in healthy offspring of hypertensive parents.

Essential hypertension is associated with increased plasma leptin levels and decreased human soluble leptin receptor (hsLR) concentration. The aim of this study was to determine whether the concentration of hsLR differs among offspring of hypertensive compared with nonhypertensive parents. Subjects in the 2 groups were matched for age, sex, and body mass index. Forty-six (24 male, 22 female; mean age, 18+/-3 years; body mass index, 22.4+/-1.4 kg/m2) healthy offspring of hypertensive parents (group A) and 50 (28 male, 22 female; mean age, 18+/-3.2 years; body mass index, 22.6+/-1.7 kg/m2) healthy offspring of healthy parents (group B) were studied. The hsLR concentration (enzyme-linked immunosorbent assay method) and leptin plasma levels (radioimmunoassay method) were determined in the study population. Plasma leptin levels were significantly higher (10+/-5 vs 6+/-3 ng/mL; P<.001), while hsLR concentration was significantly lower (20+/-7 vs 29+/-8 U/mL; P<.001) in group A compared with group B. Our findings suggest that offspring of hypertensive parents have significantly higher plasma leptin levels and significantly lower hsLR concentrations compared with healthy offspring of healthy normotensive parents. Further studies are needed to determine the clinical significance of these observations.

Mechanical behavior of colonic anastomosis in experimental settings as a measure of wound repair and tissue integrity.

AIM: To determine the mechanical properties of anastomotic colonic tissue in experimental settings and therefore give a measure of wound healing. METHODS: Thirty-six male Wistar rats were used as experimental models of anastomotic tissue integrity. On the 5th post-operative day, the tensile strength was measured by application of an axial force, providing a quantitative measure of anastomotic dehiscence and leakage. RESULTS: Diagrams of the load as a function of the time [P = P (t)] and of the displacement also as a function of time [Delta s = Delta s (t)] were recorded for each test, permitting the design of the load versus the displacement diagram and thus providing significant data about the critical values of anastomotic failure. Quantitative data were obtained concerning the anastomotic strength of both control specimens (healthy rats), as well as specimens from non-healthy rats for comparison. CONCLUSION: This experimental model provides an excellent method of measuring anastomotic strength. Despite the relative small number of specimens used, this method provides an accurate way of measuring wound repair. More experimental measurements need to be performed to correlate emerging tensile strength values to anastomotic failure.

Correlation between oxidative stress and immunosuppressive therapy in renal transplant recipients with an uneventful postoperative course and stable renal function.

BACKGROUND: Reactive oxygen species (ROS) are important mediators of cellular damage and lipid peroxidation is the most important expression of ROS-induced oxidative stress. Recent studies have suggested that increased plasma malondialdehyde (MDA) levels are a consequence of specific immunosuppressive therapies. This study aims at investigating the relation between oxidative stress and immunosuppressive therapies in renal transplant patients with stable renal function and uneventful postoperative course. METHODS: The study group included 26 renal patients. Two groups of renal transplant recipients, treated with a different combination of immunosuppressive agents were studied (Group A: CyA, MMF, Steroids and Basiliximab, Group B: Tacrolimus, MMF, Steroids and Daclizumab). All patients had an uneventful postoperative course. Plasma MDA levels were measured before transplantation, 1 and 6 months after. Plasma concentration of endogenous creatinine (Cr) was used as a measure of stable renal function. RESULTS: Levels of MDA were increased before the transplantation in all renal patients (MDA: 7.81 +/- 4.81, normal levels: 2.23-4.08 nmol/ml, P < 0.05). Combined therapy with CyA was associated with high values of MDA at 6 months measurement after transplantation. However this tendency of increased MDA levels did not achieve a statistical significance (Group A: 6.97 vs. 9.06 nmol/ml, P>0.05). On the contrary, statistically significant diminution of MDA levels was observed in Group B patients (Tacrolimus-MMF-steroids) at 6 months measurement after transplantation. (Group B: 8.61 vs. 4.11 nmol/ml, P<0.02<0.05). CONCLUSIONS: Immunosuppressive combined therapy with CyA was associated with the high values of MDA that were measured posttransplantly. Our study provides strong evidence that Tacrolimus is significantly associated with improved free radical metabolism.

Adiponectin and resistin plasma levels in healthy individuals with prehypertension.

Prehypertension seems to be related to increased cardiovascular risk in healthy subjects, while hypoadiponectinemia and hyperresistinemia may contribute to insulin resistance and accelerated atherogenesis. This study investigated whether plasma levels of adiponectin (known to increase insulin sensitivity) and resistin (a protein possibly involved in inflammatory activities) are affected in healthy individuals with prehypertension, and to compare the findings to those of healthy normotensives matched for age, gender, and body mass index. Twenty-six (14 men and 12 women) healthy individuals with prehypertension (mean age, 52+/-5 years; mean body mass index, 23+/-1.5 kg/m2) and 24 healthy normotensives (13 men and 11 women; mean age 53+/-6 years; body mass index 23.2+/-1.4 kg/m2) were studied. The adiponectin and resistin plasma levels were determined by the enzyme-linked immunosorbent assay method. Plasma resistin levels were significantly higher, while adiponectin plasma levels were significantly lower, in prehypertensive subjects compared with normotensive subjects (10.62+/-3.17 ng/mL vs. 6.72+/-3.15 ng/mL and 6.26+/-2.18 mg/mL vs. 12.12+/-4.8 mg/mL; p < 0.01, respectively). The findings suggest that healthy individuals with prehypertension have significantly higher resistin plasma levels and significantly lower adiponectin plasma levels compared with healthy normotensives. These findings may represent another possible mechanism that may increase the cardiovascular risk in this special group of patients, needing further investigation.

Changes in metalloproteinases in healthy normotensive patients with high-normal blood pressure.

INTRODUCTION: High-normal blood pressure (HNBP) seems to be related to increased cardiovascular risk in healthy, normotensive subjects, while essential hypertension is associated with an increase in extracellular matrix content, especially fibrillar collagen type I. The aim of our study was to investigate whether collagen degradation is altered in healthy normotensives with HNBP, and whether this alteration could be related to disturbances in the matrix metalloproteinases plasma concentration, and to compare the findings to those of healthy normotensives with normal blood pressure (NBP) levels, matched for age, sex and BMI. METHODS: Twenty six (14 males, 12 females) healthy, normotensive patients with HNBP, mean age 52 +/- 5 yrs, and BMI 23 +/- 1.5 kg/m(2) (group A), and 24, healthy normotensive patients (13 males, 11 females) with NBP, mean age 53 +/- 6 yrs, and BMI 23.2 +/- 1.4 kg/m(2) (group B), were studied. The two groups were matched for age, sex and BMI. Plasma levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitors (TIMP-1) and (TIMP-4) were determined by relevant ELISA in the study population. RESULTS: Plasma MMP-9 levels were significantly higher, while TIMP-1 and TIMP-4 levels were significantly lower in group A compared to group B, (MMP-9 579 +/- 147 versus 294 +/- 111 ng/mL, TIMP-1 178 +/- 45 versus 237 +/- 35 ng/mL p < 0.01, and TIMP-4 2.2 +/- 1.4 versus 4.4 +/- 2.1 p < 0.04 respectively). CONCLUSIONS: Our findings suggest that healthy normotensives with high-normal blood pressure have significantly increased MMP-9 and decreased TIMP-1 and TIMP-4 plasma levels compared to healthy normotensives with normal blood pressure. These findings need further investigation.

Human soluble leptin receptor number in healthy normotensive individuals with high normal blood pressure.

BACKGROUND: High normal blood pressure (BP) seems to be related to increased cardiovascular risk in healthy normotensive subjects, whereas hyperleptinemia enhances both sympathetic tone and arterial BP. The aim of our study was to determine the human soluble leptin receptor number in healthy normotensive subjects with high normal BP and to compare these findings to those of healthy normotensive individuals with normal BP levels. METHODS: We studied 36 healthy normotensive individuals with high normal BP (19 men and 17 women, mean age 42+/-8 years, body mass index [BMI] 23+/-1.5 kg/m2) and 40 healthy normotensive individuals with normal BP (23 men and 17 women, mean age 43+/-7 years, BMI 23.2+/-1.4 kg/m2). The two groups are matched for age, sex, and BMI. The human soluble leptin receptor number and immunoreactive leptin levels were determined in the study population by enzyme-linked immunoassay and radioimmunoassay, respectively. RESULTS: Mean plasma leptin levels were significantly higher, whereas mean human soluble leptin receptor numbers were lower in the group with high normal BP compared with the normotensive group (10+/-4.8 v 6+/-2.7 ng/mL, P<.001 and 18+/-7 v 27+/-9 IU/mL, P<.001, respectively). CONCLUSIONS: Our findings indicate that normotensive individuals with high normal BP have statistically significantly higher plasma leptin levels and lower numbers of human soluble leptin receptors. This observation may play a important role in the pathogenesis of cardiovascular events in this special group of patients and needs further investigation.

Serum levels of the senescence biomarker clusterin/apolipoprotein J increase significantly in diabetes type II and during development of coronary heart disease or at myocardial infarction.

Clusterin/apolipoprotein J (hereafter ApoJ) is a conserved secreted glycoprotein expressed by a wide array of tissues and being implicated in several physiological processes. ApoJ has been shown to associate with both normal in vitro aging, namely replicative senescence, as well as with stress induced premature senescence. In vivo, the protein is up-regulated in many severe physiological disturbances that relate to advanced aging, including accumulation in the artery wall during the development of atherosclerosis. In the current report we have expanded our previous studies that focus in the biological role of ApoJ during aging by addressing two interrelated issues: (a) we have examined the potential ApoJ association with in vivo aging and (b) we have studied whether its accumulation in the artery wall during the development of atherosclerosis is combined with a measurable increase of its serum levels, as well as, whether a similar effect occurs in diseases, such as diabetes type II, known to represent major risk factors of atherosclerosis. By combining a sandwich ELISA assay and immunoblotting analysis we demonstrate a measurable increase of ApoJ serum levels with age in males and provide evidence that, as compared to healthy donors, the serum ApoJ amount increases significantly in diabetic type II patients and in patients suffering from either a developing coronary heart disease, or myocardial infarction. The highest serum ApoJ levels were found during myocardial infarction but no correlation was observed with the number of vessels with documented atherosclerotic damage. In conclusion, this report illustrates that ApoJ accumulation in serum is probably coupled to a generalized stress mediated induction mechanism that is specifically related to certain diseases; moreover these data raise the possibility that elevated ApoJ levels in serum may represent a strong indication of vascular damage.