Correlation of Atrial Natriuretic Peptide and Cyclic Guanosine Monophosphate Plasma Concentrations in Patients with Heart Disorders During Rest and Exercise

Peer Reviewe

Fractionation of an Extract of Pluchea odorata Separates a Property Indicative for the Induction of Cell Plasticity from One That Inhibits a Neoplastic Phenotype

Introduction. Several studies demonstrated that anti-inflammatory remedies exhibit excellent anti-neoplastic properties. An extract of Pluchea odorata (Asteraceae), which is used for wound healing and against inflammatory conditions, was fractionated and properties correlating to anti-neoplastic and wound healing effects were separated. Methods. Up to six fractionation steps using silica gel, Sephadex columns, and distinct solvent systems were used, and eluted fractions were analysed by thin layer chromatography, apoptosis, and proliferation assays. The expression of oncogenes and proteins regulating cell migration was investigated by immunoblotting after treating HL60 cells with the most active fractions. Results. Sequential fractionations enriched anti-neoplastic activities which suppressed oncogene expression of JunB, c-Jun, c-Myc, and Stat3. Furthermore, a fraction (F4.6.3) inducing or keeping up expression of the mobility markers MYPT, ROCK1, and paxillin could be separated from another fraction (F4.3.7), which inhibited these markers. Conclusions. Wound healing builds up scar or specific tissue, and hence, compounds enhancing cell migration support this process. In contrast, successful anti-neoplastic therapy combats tumour progression, and thus, suppression of cell migration is mandatory

A Sex-Specific Analysis of the Predictive Value of Troponin I and T in Patients With and Without Diabetes Mellitus After Successful Coronary Intervention

Background: Elevated levels of troponin are associated with future major adverse cardiac events (MACE). Data on the prognostic value of high sensitive troponin T (hs-TnT) compared to high sensitive troponin I (hs-TnI) in diabetic and non-diabetic patients are sparse.Methods: We analyzed patients of a single-center registry undergoing coronary stenting between 2003 and 2006. As a primary endpoint we assessed MACE, a composite of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke according to sex and diabetes status using log-rank. As a second endpoint, we assessed the prognostic impact of hs-TnT and hs-TnI on MACE, adjusting for known confounders using Cox regression analysis.Results: Out of 818 investigated patients, 267 (32.6%) were female. Diabetes mellitus type 2 (T2DM) was diagnosed in 206 (25.2%) patients.After a mean follow-up of 6.6 ± 3.7 years, MACE occurred in 235 (28.7%) patients. The primary endpoint components of cardiovascular death occurred in 115 (14.1%) patients, MI in 75 (9.2%), and ischemic stroke in 45 (5.5%). Outcomes differed significantly according to sex and diabetes status (p = 0.003). In descending order, MACE rates were as follows: female diabetic patients (40.8%), female non-diabetic patients (32.7%), male diabetic patients (28.9%), and male non-diabetic patients (24.8%). Additionally, females with diabetes were at higher risk of cardiovascular death compared to diabetic men (28 vs. 15%). Hs-TnI (HR 1.477 [95% CI 1.100–1.985]; p = 0.010) and hs-TnT (HR 1.615 [95%CI 1.111–2.348]; p = 0.012) above the 99th percentile were significantly associated with MACE. Both assays showed tendency toward association with MACE in all subgroups.Conclusion: Diabetic patients, particularly females, with known coronary artery disease had a higher risk of subsequent MACE. Both, hs-TnI and hs-TnT significantly correlated with MACE

Endostatin and osteopontin are elevated in patients with both coronary artery disease and aortic valve calcification

Background: The angiostatic factor endostatin (ES) plays an important role as mediator of angiogenesis. Elevated osteopontin (OPN) was associated with valve calcification in healthy individuals. The present study aimed to investigate ES and OPN levels in patients with both coronary artery disease (CAD) and aortic valve calcification (AVC). Methods and results: In total 224 non- or ex-smoking patients (161 male, mean age: 61.09 ± 11.02 years; 63 female: mean age: 67.49 ± 7.87 years) with angiographically verified and quantified CAD were recruited. Serum ES and plasma OPN levels were measured by ELISA and AVC was evaluated by a parasternal short axis view and quantified as non-, mild or moderate/severe. There was a stepwise increase of ES measurable with increasing severity of AVC, independent from age, BMI and CAD-severity (p = 0.018; F = 4.09). OPN also increased significantly with the grade of AVC severity (p = 0.029; F = 3.61) but was no longer significant when the co-variables (p = 0.31; F = 1.18) were inserted. Conclusions: This is the first study showing an association of ES with AVC in CAD-patients independent from age, BMI and CAD-severity which seems to be of distinct interest when trying to understand the process of heart valve calcification. OPN also correlates with AVC-severity but is mostly dependent on the age of the patients

Heart and Vessels / Long-term physical activity leads to a significant increase in serum sRAGE levels : a sign of decreased AGE-mediated inflammation due to physical activity?

There is growing evidence that low levels of the circulating soluble receptor of advanced glycation end products (sRAGE) are a valuable predictor of cardiovascular disease (CVD). The aim of this prospective study was to investigate the influence of long-term physical activity on serum sRAGE levels. 109 subjects were recruited, and 98 completed the study. Participants were asked to perform exercise within the calculated training pulse for 8 months. The performance gain was measured/quantified by bicycle stress tests at the beginning and end of the observation period. sRAGE was measured at baseline and after 2/6/8 months by ELISA. Backwards, multiple linear regression analysis was performed to investigate the association of co-variables age, sex, BMI, and performance at baseline, HbA1c, and lipoprotein a with baseline sRAGE levels. We identified BMI and lipoprotein a as significant predictors for baseline sRAGE levels. Compared to subjects with a performance gain 4.9% subjects with a gain > 5% showed a significant increase in sRAGE levels up to 22%. sRAGE serum levels correlate negatively with lipoprotein a levels and BMI and long-term physical activity leads to a significant increase in serum sRAGE levels (922%), whereby the sRAGE increase is most pronounced in subjects with initially low-performance levels, suggesting that in particular, these subject profit the most from increased physical activity. The sport-mediated increase of sRAGE might be a sign of decreased AGE-mediated inflammation and highlight the protective effect of sports on CVD and other disease which are at least partly mediated by an increased inflammation status. Clinical trials registration NCT02097199.(VLID)359103

Endurance training significantly increases serum endocan but not osteoprotegerin levels: a prospective observational study

Background Endocan (EN) was suggested a potential inflammatory and cardiovascular disease (CVD) marker which might also be involved in renal failure and/or renal failure-associated vascular events. It is not clear whether osteoprotegerin (OPG) is a pro- or anti-atherogenic factor, however, it is agreed upon that OPG is elevated in subjects with increased calcification status. The aim of the study was to investigate the influence of long-term physical activity on serum endocan (EN) and osteoprotegerin-levels. Methods One hundred nine subjects were told to increase their amount of physical activity for 8 months by performing 150min/week moderate or 75min/week vigorous exercise. Incremental cycle ergometer tests were performed at the beginning and the end of the study to prove and quantify the performance gain. Blood samples were drawn at baseline and every 2 months for the determination of EN and OPG. To investigate the difference between baseline and 8 months levels of EN and OPG we used a paired sample t-test. To investigate the significance of the tendency of the progression (baseline/2 months/4 months/6 months/8 months) we used a Friedman test. Results Thirty-eight female and 60 male subjects completed the study. In the group of 61 subjects who had a performance gain by >4,9% EN-levels increased from 146 110 to 196 238 pg/ml (p = 0,036) equivalent to an increase of 33,5% but there was no significant change in OPG (4,4 2,4 pmol/l vs. 4,3 2,1 pmol/l; p = 0,668). Conclusions Physical activity increases significantly EN-levels relativizing the status of EN as proinflammatory factor. EN should rather be considered as a mediator which is involved in several physiological (e.g., angiogenesis) but also pathological processes (e.g., CVD, tumour progression or endothelium-dependent inflammation) and whose expression can be significantly influenced by long term endurance training.(VLID)484340

International Journal of Medical Sciences / Sports and HDL-Quality Reflected By Serum Amyloid A and Surfactant Protein B

Background: The aim of this prospective study was to investigate the influence of long-term physical activity on HDL quality, reflected by serum amyloid A (SAA) and surfactant protein B (SPB). Methods and results: 109 healthy subjects were recruited, 98 completed the study. Participants perform within the calculated training pulse for 8 months. The performance gain was measured/quantified by bicycle stress tests at the beginning and end of the observation period. SAA and SPB were measured at baseline and after 4 and 8 months by ELISA. In contrary to HDL-quantity, there was no sports-induced change in SAA or SPB observable. However, significant predictors for SPB-levels were smoking status, BMI and weekly alcohol consumption and for SAA weekly alcohol consumption together with sex and hsCRP-levels. Conclusions: Long-term physical activity increases HDL-quantity but has no impact on HDL-quality reflected by SAA and SPB. Smoking is associated with higher SPB-levels and the weekly alcohol intake is associated with both higher SAA and SPB-levels suggesting a damaging effect of smoking and drinking alcohol on the HDL-quality. We assume that HDL-quality is at least as important as HDL-quantity when investigating the role of HDL in (cardiovascular) disease and should receive attention in further studies dealing with HDL.(VLID)486411

Physical Exercise Promotes DNase Activity Enhancing the Capacity to Degrade Neutrophil Extracellular Traps

(1) Background: An unhealthy lifestyle is a significant contributor to the development of chronic diseases. Physical activity can benefit primary and secondary prevention. Higher DNase activity is associated with favourable outcomes after cardiovascular (CV) events. In this study, we aimed to investigate the influence of consequent endurance exercise on DNase activity. (2) Methods: 98 subjects with at least one CV risk factor but the physical ability to perform endurance training were included. Individuals performed a bicycle stress test at the beginning and after 8 months to assess physical performance. In between, all participants were instructed to engage in guideline-directed physical activity. Blood samples were drawn in two-month intervals to assess routine laboratory parameters, cell-free DNA (cfDNA), and DNase activity. (3) Results: Prevailing CV risk factors were overweight (65.9%), a positive family history (44.9%), hypertension (32.7%) and smoking (20.4%). Performance changed by 7.8 ± 9.1% after 8 months. Comparison of baseline to 8 months revealed a decrease in cfDNA and an increase in DNase activity. This effect was driven by participants who achieved a performance gain. (4) Conclusions: Regular physical activity might improve CV health by increasing DNase activity and thereby, the capacity to lower pro-inflammatory signalling, complementing measures of primary and secondary prevention

Metabolism of estrogens

High-grade serous ovarian cancer (HGSOC) is currently treated with cytoreductive surgery and platinum-based chemotherapy. The majority of patients show a primary responsehowever, many rapidly develop drug resistance. Antiestrogens have been studied as low toxic treatment options for HGSOC, with higher response rates in platinum-sensitive cases. Mechanisms for this difference in response remain unknown. Therefore, the present study investigated the impact of platinum resistance on steroid metabolism in six established HGSOC cell lines sensitive and resistant against carboplatin using a high-resolution mass spectrometry assay to simultaneously quantify the ten main steroids of the estrogenic metabolic pathway. An up to 60-fold higher formation of steroid hormones and their sulfated or glucuronidated metabolites was observed in carboplatin-sensitive cells, which was reversible by treatment with interleukin-6 (IL-6). Conversely, treatment of carboplatin-resistant cells expressing high levels of endogenous IL-6 with the monoclonal anti-IL-6R antibody tocilizumab changed their status to "platinum-sensitive", exhibiting a decreased IC$_{50}$ value for carboplatin, decreased growth, and significantly higher estrogen metabolism. Analysis of these metabolic differences could help to detect platinum resistance in HGSOC patients earlier, there by allowing more efficient interventions