Connection between Telomerase Activity in PBMC and Markers of Inflammation and Endothelial Dysfunction in Patients with Metabolic Syndrome

Metabolic syndrome (MS) is a constellation of metabolic derangements associated with vascular endothelial dysfunction and oxidative stress and is widely regarded as an inflammatory condition, accompanied by an increased risk for cardiovascular disease. The present study tried to investigate the implications of telomerase activity with inflammation and impaired endothelial function in patients with metabolic syndrome. Telomerase activity in circulating peripheral blood mononuclear cells (PBMC), TNF-α, IL-6 and ADMA were monitored in 39 patients with MS and 20 age and sex-matched healthy volunteers. Telomerase activity in PBMC, TNF-α, IL-6 and ADMA were all significantly elevated in patients with MS compared to healthy volunteers. PBMC telomerase was negatively correlated with HDL and positively correlated with ADMA, while no association between TNF-α and IL-6 was observed. IL-6 was increasing with increasing systolic pressure both in the patients with MS and in the healthy volunteers, while smoking and diabetes were positively correlated with IL-6 only in the patients' group. In conclusion, in patients with MS characterised by a strong dyslipidemic profile and low diabetes prevalence, significant telomerase activity was detected in circulating PBMC, along with elevated markers of inflammation and endothelial dysfunction. These findings suggest a prolonged activity of inflammatory cells in the studied state of this metabolic disorder that could represent a contributory pathway in the pathogenesis of atherosclerosis

Leukocyte Telomere Length in Major Depression: Correlations with Chronicity, Inflammation and Oxidative Stress - Preliminary Findings

Depression is associated with an unusually high rate of aging-related illnesses and early mortality. One aspect of “accelerated aging” in depression may be shortened leukocyte telomeres. When telomeres critically shorten, as often occurs with repeated mitoses or in response to oxidation and inflammation, cells may die. Indeed, leukocyte telomere shortening predicts early mortality and medical illnesses in non-depressed populations. We sought to determine if leukocyte telomeres are shortened in Major Depressive Disorder (MDD), whether this is a function of lifetime depression exposure and whether this is related to putative mediators, oxidation and inflammation.Leukocyte telomere length was compared between 18 unmedicated MDD subjects and 17 controls and was correlated with lifetime depression chronicity and peripheral markers of oxidation (F2-isoprostane/Vitamin C ratio) and inflammation (IL-6). Analyses were controlled for age and sex.The depressed group, as a whole, did not differ from the controls in telomere length. However, telomere length was significantly inversely correlated with lifetime depression exposure, even after controlling for age (p<0.05). Average telomere length in the depressed subjects who were above the median of lifetime depression exposure (≥9.2 years' cumulative duration) was 281 base pairs shorter than that in controls (p<0.05), corresponding to approximately seven years of “accelerated cell aging.” Telomere length was inversely correlated with oxidative stress in the depressed subjects (p<0.01) and in the controls (p<0.05) and with inflammation in the depressed subjects (p<0.05).These preliminary data indicate that accelerated aging at the level of leukocyte telomeres is proportional to lifetime exposure to MDD. This might be related to cumulative exposure to oxidative stress and inflammation in MDD. This suggest that telomere shortening does not antedate depression and is not an intrinsic feature. Rather, telomere shortening may progress in proportion to lifetime depression exposure

Detection of Chlamydia pneumoniae in peripheral blood mononuclear cells: correlation with inflammation and atherosclerosis in haemodialysis patients

Background. Chlamydia pneumoniae has been implicated as an inflammatory agent in atherosclerosis. Clinical studies in this field have yielded conflicting results, which may have resulted from a lack of standardization for C. pneumoniae detection. We attempted to accurately estimate C. pneumoniae prevalence and to examine whether C. pneumoniae is associated with atherosclerosis and inflammation in haemodialysis (HD) patients. To do this, we assessed C. pneumoniae presence by a combination of methods and correlated its levels with inflammatory and atherosclerotic indexes in these patients. Methods. Chlamydia pneumoniae was identified by polymerase chain reaction (PCR) in DNA extracted from cell cultures inoculated with patient buffy coats and by serum IgG antibodies against C. pneumoniae (IgGCp). Inflammation was assessed by C-reactive protein and serum amyloid A and atherosclerosis was evaluated from clinical and laboratory data. Results. Of the 130 patients, only nine had viable C. pneumoniae in peripheral blood mononuclear cells (PBMCs) while 64 had serum IgGCp. Although patients with viable C. pneumoniae had higher atherosclerotic scores, seropositive and negative patients showed similar scores. Patients with atherosclerosis exhibited higher inflammatory indexes. Neither patients with detectable C. pneumoniae in PBMCs nor seropositive subjects had higher inflammation than negative patients. Conclusions. We found that viable C. pneumoniae in PBMCs, assessed by cell culture and PCR, was present in a small percentage of HD patients and was correlated with atherosclerosis. Seropositivity was much higher in HD patients but was not associated with viable C. pneumoniae or with atherosclerosis. Further studies in HD patients using high sensitivity and specificity methods in larger populations will be necessary to clarify the relationship between C. pneumoniae and atherosclerosis

Serum and peripheral blood mononuclear cells infectious burden: Correlation to inflammation and atherosclerosis in haemodialysis patients

Background: Infectious agents may be implicated in the inflammatory atherosclerotic process. Not only specific microorganisms but also the infectious burden, defined as the number of pathogens to which a patient is exposed, has been associated with atherosclerosis. In the present study, the infectious burden, determined directly (by identification of viable pathogens in peripheral blood mononuclear cells (PBMC)) and indirectly (by serum antibodies detection) is correlated to the inflammatory and atherosclerotic status in haemodialysis (HD) patients, a population at high risk for cardiovascular disease. Methods: The viable forms of four microorganisms (Chlamydia pneumoniae, herpes virus 1 and 2 and cytomegalovirus) were identified in patients PBMC by cell cultures and subsequent polymerase chain reaction. Serum IgG against the above pathogens and Helicobacter pylori were also determined. Inflammation was assessed by measurement of C-reactive protein (CRP), serum amyloid A (SAA), three pro- and one anti-inflammatory cytokines and four adhesion molecules. Atherosclerosis was defined by a scoring system using medical history data. Results: The number of viable pathogens identified in PBMC in the 122 HD patients included in the study were zero in 22.1% of them, one in 33.6%, two in 43.4% and three in one patient. The number of IgG antibodies determined was one in 6.6% of patients, two in 32%, three in 48.4% and four in 13.1%. Seropositivity was not significantly different between patients with or without the respective viable pathogen identified in PBMC. Atherosclerosis was present in 40.2% of patients, and CRP, SAA and interleukin-6 were all increased in these patients. Neither inflammatory indexes nor atherosclerosis were significantly different in patients with a higher number of viable pathogens detected in PBMC or in those with a higher antibodies number. Conclusions: The direct infectious burden determination (the number of viable pathogens in PBMC) does not coincide with the serum (by IgG detection) infectious burden. Although inflammation correlates to atherosclerosis, neither PBMC nor the serum infectious burden is associated with these two entities in the inflamed and atherosclerotic HD patients

Low cholesterol along with inflammation predicts morbidity and mortality in hemodialysis patients

Low and not high cholesterol seems to predict high mortality in hemodialysis (HD) patients. The confirmation of this reverse epidemiology as well as its possible interconnection with the increased inflammatory activity observed in this population is being explored in the present study. A group of 136 HD patients was prospectively studied for 2 years, and cardiovascular disease (CVD) as well as all-cause mortality and morbidity were recorded. Baseline lipid profile, inflammatory status, and patients&apos; characteristics were studied as potential survival and hospitalization predictors. During the 24-month follow-up, 21 deaths (52.4% due to CVD) and 38 hospitalizations (55.3% due to CVD) were recorded. In multivariate Cox regression analysis, decreased interleukin-10 (IL-10) and decreased total serum cholesterol (TChol) were the only independent predictors of CVD mortality while C-reactive protein and decreased TChol predicted all-cause mortality. Interleukin-10 at baseline was 11.29 ± 21.49 vs. 5.51 ± 4.57 pg/mL (P &lt; 0.018) and TChol 167.37 ± 47.84 vs.122.04 ± 26.48mg/dL (P &lt; 0.000) in survivors vs. nonsurvivors from CVD, while C-reactive protein at baseline was 9.37 ± 11.54 vs. 23.15 ± 18.76mg/L (P &lt; 0.000) and TChol 169.26 ± 46.42 vs. 133.26 ± 46.33 mg/dL (P &lt; 0.003) in survivors vs. nonsurvivors from any cause of death. Using the same method of statistical analysis, IL-6 and decreased soluble gp130 (sgp130)-an antagonist of IL-6 action-were found to be the only independent prognostic factors for hospitalization due to CVD while decreased soluble gp130 remained the sole predictor of hospitalization due to any cause. In conclusion, reverse epidemiology regarding cholesterol is confirmed in the present study. Furthermore, inflammatory activity also predicts, independently of or in conjunction with low-cholesterol, CVD and all-cause morbidity and mortality in HD patients. © Journal compilation © 2009 International Society for Hemodialysis

Transcription of the tumor suppressor genes p53 and rb in lymphocytes from patients with chronic kidney disease: Evidence of molecular senescence?

Patients suffering from renal failure exhibit an impaired immune system function. We wanted to investigate the transcription of the tumor suppressor genes p53 and RB to record, if these cells could be stimulated in vitro in order to divide, after the addition of antigenic and inflammatory factors. This expression was measured by real-time PCR in peripheral blood mononuclear cells (PBMCs) from three different groups: ten healthy individuals, ten patients with chronic kidney disease (CKD), and ten dialysis patients with end stage renal disease (ESRD). The transcription rate of these genes was also measured after the cultivation of PBMCs under four different conditions: just with the culture medium, with lipopolysaccharide (LPS), with C-reactive protein (CRP), and with lipoxin A(LXA-LPS. Our results show that in most cases after the cultivation with additives, the transcription levels were higher in dialysis patients compared to those of the other two groups. Our findings serve as indications of cellular senescence on a molecular level, while it seems that these cells are less easily stimulated in vitro in order to duplicate. © 2012 Vasileios Kordinas et al