Effects of protease activated receptor (PAR)2 blocking peptide on endothelin-1 levels in kidney tissues in endotoxemic rat mode.

AIMS: Septic shock, the severe form of sepsis, is associated with development of progressive damage in multiple organs. Kidney can be injured and its functions altered by activation of coagulation, vasoactive-peptide and inflammatory processes in sepsis. Endothelin (ET)-1, a potent vasoconstrictor, is implicated in the pathogenesis of sepsis and its complications. Protease-activated receptors (PARs) are shown to play an important role in the interplay between inflammation and coagulation. We examined the time-dependent alterations of ET-1 and inflammatory cytokine, such as tumor necrosis factor (TNF)-α in kidney tissue in lipopolysaccharide (LPS)-induced septic rat model and the effects of PAR2 blocking peptide on the LPS-induced elevations of renal ET-1 and TNF-α levels. MAIN METHODS: Male Wistar rats at 8 weeks of age were administered with either saline solution or LPS at different time points (1, 3, 6 and 10h). Additionally, we treated LPS-administered rats with PAR2 blocking peptide for 3h to assess whether blockade of PAR2 has a regulatory role on the ET-1 level in septic kidney. KEY FINDINGS: An increase in ET-1 peptide level was observed in kidney tissue after LPS administration time-dependently. Levels of renal TNF-α peaked (around 12-fold) at 1h of sepsis. Interestingly, PAR2 blocking peptide normalized the LPS-induced elevations of renal ET-1 and TNF-α levels. SIGNIFICANCE: The present study reveals a distinct chronological expression of ET-1 and TNF-α in LPS-administered renal tissues and that blockade of PAR2 may play a crucial role in treating renal injury, via normalization of inflammation, coagulation and vaso-active peptide.

Metabolic syndrome among pre- and post-menopausal rural women in Bangladesh: result from a population-based study.

BACKGROUND: Prevalence of non-communicable diseases are a challenging problems among menopausal women specially in a least developed country like Bangladesh, where majority of women suffering from at least one chronic diseases after menopausal age. So, the main objective of this study was to determine the prevalence of metabolic syndrome and related risk factors in Bangladeshi pre- and post-menopausal women living in the rural setting. METHODS: This study is based on a community based cross-sectional survey among 1802 rural women aged ≥15 years. Metabolic syndrome was defined according to the criteria of NCEP-ATP III. Logistic regression was used to estimate the association between menopausal status and metabolic syndrome and its components. RESULTS: Metabolic syndrome was presented in 25.6% respondents and it was more prevalent among post-menopausal (39.3%) as compared to pre-menopausal (16.8%) women. Logistic regression analysis reveals that prevalence of metabolic syndrome was 1.78 times higher in post-menopausal women than pre-menopausal women (P = 0.001). Prevalence of high blood pressure, elevated fasting blood glucose, and high triglyceride were significantly higher in post-menopausal women than pre-menopausal women (P < 0.05). However, prevalence of low high-density lipoprotein cholesterol was significantly lower in post-menopausal women than pre-menopausal women (P < 0.001). CONCLUSIONS: Metabolic syndrome seems to be a major health problem among post-menopausal women in many developing countries like Bangladesh and proper policy emphasis should be given on its prevention and control.

The role of angiogenic factors and their soluble receptors in acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS) associated with critical illness.

BACKGROUND: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by a disruption of the endothelium and alveolar epithelial barriers involving increased microvascular permeability, thus resulting in the set of protein-rich pulmonary edema. Angiogenic factors and their receptors, including vascular endothelial growth factor (VEGF)/VEGF-receptor (VEGFR) and the angiopoietin (Ang)/Tie2 signaling pathways, play pivotal roles in both angiogenesis and microvascular permeability. The aim of the study was to assess the relationship between angiogenic factors, their soluble receptors and ALI/ARDS associated with critically ill patients, including sepsis, severe trauma, and post-cardiac arrest syndrome (PCAS). METHODS: One hundred fifty-nine critically ill patients, including 50 patients with sepsis, 57 patients with severe trauma and 52 resuscitated after out-of-hospital cardiac arrest, were divided into three subgroups: including 25 ALI patients, 101 ARDS patients and 22 non-ALI/ARDS patients. The serum levels of angiogenic factors were measured at the time of admission (day 1), as well as day 3 and day 5 and then were compared among the ALI, ARDS and non-ALI/ARDS groups. Their predictive values for developing ALI/ARDS and 28-day mortality were evaluated. RESULTS: Higher levels of sVEGFR1 and Ang2 were observed in the ALI and ARDS patients than in the non-ALI/ARDS patients during the entire study period. The Ang2/Ang1 ratio in the ARDS group was also significantly higher than that in the non-ALI/ADRS group. The sVEGFR2 levels in the ARDS group on day 1 were significantly lower than those of the non-ALI/ADRS group. In addition, significant positive correlations were seen between the sVEGFR1, Ang2, Ang2/Ang1, and the development of ALI/ARDS in critical illness. There were also significant negative correlations between the minimal value of sVEGFR2, the maximal value of Ang1 and the ALI/ARDS group. In particular, sVEGFR2 and Ang2 were independent predictors of developing ALI/ARDS. Moreover, Ang2 and sVEGFR2 also independently predicted the mortality in ALI/ARDS patients. CONCLUSIONS: Angiogenic factors and their soluble receptors, particularly sVEGFR2 and Ang2, are thus considered to be valuable predictive biomarkers in the development of ALI/ARDS associated with critical illness and mortality in ALI/ARDS patients.

Association of age at menarche with metabolic syndrome and its components in rural Bangladeshi women.

BACKGROUND: Early age at menarche is associated with increased risk of metabolic syndrome in both China and the West. However, little is known about the impact of age at menarche and metabolic syndrome in South Asian women, including those from low-income country, where age at menarche is also falling. The aim of the present study was to investigate whether age at menarche is inversely associated with metabolic syndrome in Bangladeshi women, who are mostly poor and have limited access to and or poor health care facilities. METHODS: This community-based cross-sectional study was performed using 1423 women aged between 15-75 years from rural Bangladesh in 2009 and 2010. Metabolic syndrome was defined according to standard NCEP-ATP III criteria. Logistic regression was used to estimate the association between age at menarche and metabolic syndrome, with adjustment of potential confounding variables, including age, education, marital status, tobacco users, use of contraceptives and number of pregnancies. RESULTS: Early onset of menarche (<12 years) as compared to late onset (>13 years) was found to be associated with a higher prevalence of metabolic syndrome (odds ratio=1.55; 95 % confidence interval =1.05-2.30). Age at onset of menarche was also inversely associated with prevalence of high triglycerides (P for trend <0.01) and low high-density lipoprotein cholesterol (P for trend = 0.01), but positively associated with prevalence of high fasting blood glucose (P for trend =0.02). However, no significant association was found between age at menarche, high blood pressure and elevated waist circumference. CONCLUSION: Early onset of menarche might promote or trigger development of metabolic syndrome. Thus, knowledge of the history of age at onset of menarche may be critical in identifying women at risk of developing metabolic syndrome and those likely to benefit the most from early interventions.

Comprehensive assessment of metabolic syndrome among rural Bangladeshi women.

BACKGROUND: Metabolic syndrome (MS), defined as a constellation of cardiovascular disease (CVD) risk factors, is one of the fastest growing public health burdens in the Asia-Pacific region. This trend is despite the fact that people in this region are no more overweight than Europeans and Americans. Unfortunately, in South Asia, MS screening has only been performed in a few countries other than Bangladesh. Therefore the present study is designed to conduct a comprehensive screening of MS in Bangladeshi rural women, which includes estimation of prevalence and assessment of risk factor. METHODS: A total of 1535 rural Bangladesh women aged ≥ 15 years were studied using a population based cross-sectional survey. The prevalence of MS was estimated using NCEP ATP III, modified NCEP ATP III and IDF criteria. RESULTS: The prevalence rates of MS were 25.60% (NCEP ATP III), 36.68% (modified NCEP ATP III), and 19.80% (IDF), as revealed by the present study. Furthermore, based on the NCEP ATP III criteria, 11.60% of the subjects were found to have excess waist circumference; 29.12% had elevated blood pressure, 30.42% had elevated fasting plasma glucose level, 85.47% had low HDL values and 26.91% had increased triglyceride values. Low plasma HDL level was found to be the most common abnormality in the target population and elevated waist circumference was the least frequent component. CONCLUSIONS: The present study reveals a high prevalence of MS and its associated risk factors in rural Bangladeshi women. These findings are important in that they provide insights that will be helpful in formulating effective public health policy, notably the development of future health prevention strategies in Bangladesh.

Prevalence of metabolic syndrome among rural Bangladeshi women.

We assessed prevalence of metabolic syndrome (MS) in rural women of Bangladesh using 1485 women aged ≥15 years. The prevalence rate of MS was 31.25% (NCEP ATP III modified). And 85.05% population had low HDL values. These findings are important in the development of future health prevention strategies in Bangladesh.

Estrogen receptor alpha and beta are both involved in the cerebral VEGF/Akt/NO pathway and cerebral angiogenesis in female mice.

We have previously demonstrated that vascular endothelial growth factor (VEGF) is critical for cerebral angiogenesis in middle-aged female rats and may play a role in the flow-preserving neuroprotective actions of estrogen through its angiogenic and antiapoptotic properties. Here, we attempt to elucidate the effects of estrogen and the specific estrogen receptor (ER) subtype in cerebral VEGF/Akt/NO pathways and cerebral angiogenesis using 15-week old female mice that are either wild-type (WT), lack estrogen receptor α (ERαKO) or ß (ERßKO). Protein levels of VEGF and basic signaling molecules of VEGF angiogenic pathway in the frontal cortex were expressed as follows, as revealed by ELISA and immunoblotting : a) VEGF; WT: ERαKO: ERßKO, 47 ± 15: 27 ± 5: 28 ± 5 pg/mg, respectively (P < 0.01); b) KDR decreased about 40% in both ERαKO and ERßKO compared to WT; c) Akt was significantly down-regulated in both ERαKO and ERßKO compared to WT; d) phosphorylated Akt (pAkt); WT: ERαKO: ERßKO, 0.6 ± 0.2: 0.3 ± 0.01: 0.3 ± 0.1 units/mg, respectively; e) phosphorylated eNOS significantly decreased about 45% in both ERαKO and ERßKO compared to WT. Cerebral capillary density decreased in both ERαKO and ERßKO compared to WT. Thus, it can be concluded that in female mice, VEGF/Akt/eNOS pathway plays an important role in cerebral angiogenesis and that both ER subtypes are involved in the regulation of VEGF and its signaling molecule expression in the frontal cortex.

VEGF signaling is disrupted in the hearts of mice lacking estrogen receptor alpha.

Estrogen has widely been credited for cardioprotection in women. However, the exact mechanisms that underlie these beneficial estrogenic effects are not completely understood. Here, we sought to: 1) elucidate estrogen's influence on levels of vascular endothelial growth factor (VEGF), a key regulator of cardiovascular processes, and components of its basic signaling machinery (VEGF receptors, Akt, and eNOS) in the heart, and 2) delineate the specific estrogen receptor signaling pathway that mediates its beneficial effects using mice lacking either estrogen receptor alpha or estrogen receptor beta. We analyzed pattern of VEGF signaling and the associated coronary capillary density in the hearts of wild-type (WT), estrogen receptor alpha knockout (ERalpha-KO), and estrogen receptor beta knockout (ERbeta-KO) female mice. Deletion of estrogen receptor alpha causes a marked decrease in coronary capillary density compared to wild-type (WT) mice, while that of estrogen receptor beta had a minimal effect. Consistent with reduced coronary capillary density, cardiac expression levels of VEGF and its signaling molecules (two receptors, phosphorylated Akt, and eNOS) in ERalpha-KO mice were reduced to half of WT, in contrast to ERbeta-KO mice that only showed a slight decrease. Moreover, activity of eNOS was greatly lowered in ERalpha-KO mice. These data suggest that estrogen acts largely via estrogen receptor alpha to regulate VEGF transcription and possibly components of its basic signaling and ultimately, the development of coronary microvasculature in the heart. This molecular and histological data, in part, sheds some insights into potential mechanisms that may likely underlie estrogen's cardioprotective effects.